請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57253完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許金玉 | |
| dc.contributor.author | Po-Hao Chang | en |
| dc.contributor.author | 張博皓 | zh_TW |
| dc.date.accessioned | 2021-06-16T06:39:20Z | - |
| dc.date.available | 2014-10-09 | |
| dc.date.copyright | 2014-10-09 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-07-30 | |
| dc.identifier.citation | Ahima, R.S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., and Flier, J.S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature 382, 250-252.
Alajez, N.M., Lenarduzzi, M., Ito, E., Hui, A.B., Shi, W., Bruce, J., Yue, S., Huang, S.H., Xu, W., Waldron, J., et al. (2011). MiR-218 suppresses nasopharyngeal cancer progression through downregulation of survivin and the SLIT2-ROBO1 pathway. Cancer research 71, 2381-2391. Bachelot, T., Ray-Coquard, I., Menetrier-Caux, C., Rastkha, M., Duc, A., and Blay, J.Y. (2003). Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. British journal of cancer 88, 1721-1726. Barbareschi, M., Pelosio, P., Caffo, O., Buttitta, F., Pellegrini, S., Barbazza, R., Dalla Palma, P., Bevilacqua, G., and Marchetti, A. (1997). Cyclin-D1-gene amplification and expression in breast carcinoma: relation with clinicopathologic characteristics and with retinoblastoma gene product, p53 and p21WAF1 immunohistochemical expression. International journal of cancer Journal international du cancer 74, 171-174. Bashaw, G.J., Kidd, T., Murray, D., Pawson, T., and Goodman, C.S. (2000). Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor. Cell 101, 703-715. Berg, A.H., Combs, T.P., Du, X., Brownlee, M., and Scherer, P.E. (2001). The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nature medicine 7, 947-953. Bhowmick, N.A., Neilson, E.G., and Moses, H.L. (2004). Stromal fibroblasts in cancer initiation and progression. Nature 432, 332-337. Bissell, M.J., and Hines, W.C. (2011). Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nature medicine 17, 320-329. Brantley-Sieders, D.M., Dunaway, C.M., Rao, M., Short, S., Hwang, Y., Gao, Y., Li, D., Jiang, A., Shyr, Y., Wu, J.Y., et al. (2011). Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium. Cancer research 71, 976-987. Broer, S., Broer, A., Schneider, H.P., Stegen, C., Halestrap, A.P., and Deitmer, J.W. (1999). Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochemical journal. 341 ( Pt 3), 529-535. Brose, K., Bland, K.S., Wang, K.H., Arnott, D., Henzel, W., Goodman, C.S., Tessier-Lavigne, M., and Kidd, T. (1999). Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96, 795-806. Brown, L.F., Guidi, A.J., Schnitt, S.J., Van De Water, L., Iruela-Arispe, M.L., Yeo, T.K., Tognazzi, K., and Dvorak, H.F. (1999). Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clininal cancer research 5, 1041-1056. Brunn, G.J., Williams, J., Sabers, C., Wiederrecht, G., Lawrence, J.C., Jr., and Abraham, R.T. (1996). Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. The EMBO journal 15, 5256-5267. Cantley, L.C., and Neel, B.G. (1999). New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proceedings of the National Academy of Sciences of the United States of America 96, 4240-4245. Dallol, A., Forgacs, E., Martinez, A., Sekido, Y., Walker, R., Kishida, T., Rabbitts, P., Maher, E.R., Minna, J.D., and Latif, F. (2002). Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers. Oncogene 21, 3020-3028. Dallol, A., Morton, D., Maher, E.R., and Latif, F. (2003). SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells. Cancer research 63, 1054-1058. Daniel, C.W., Robinson, S., and Silberstein, G.B. (1996). The role of TGF-beta in patterning and growth of the mammary ductal tree. J Mammary Gland Biol Neoplasia 1, 331-341. Dickson, B.J., and Gilestro, G.F. (2006). Regulation of commissural axon pathfinding by slit and its Robo receptors. Annual review of cell and developmental biology 22, 651-675. Dieudonne, M.N., Machinal-Quelin, F., Serazin-Leroy, V., Leneveu, M.C., Pecquery, R., and Giudicelli, Y. (2002). Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun 293, 622-628. Dirat, B., Bochet, L., Dabek, M., Daviaud, D., Dauvillier, S., Majed, B., Wang, Y.Y., Meulle, A., Salles, B., Le Gonidec, S., et al. (2011). Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer research 71, 2455-2465. Elliott, B.E., Tam, S.P., Dexter, D., and Chen, Z.Q. (1992). Capacity of adipose tissue to promote growth and metastasis of a murine mammary carcinoma: effect of estrogen and progesterone. International journal of cancer 51, 416-424. Fan, X., Labrador, J.P., Hing, H., and Bashaw, G.J. (2003). Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline. Neuron 40, 113-127. Finak, G., Bertos, N., Pepin, F., Sadekova, S., Souleimanova, M., Zhao, H., Chen, H., Omeroglu, G., Meterissian, S., Omeroglu, A., et al. (2008). Stromal gene expression predicts clinical outcome in breast cancer. Nature medicine 14, 518-527. Fry, M.J. (2001). Phosphoinositide 3-kinase signalling in breast cancer: how big a role might it play? Breast cancer research : BCR 3, 304-312. Fukumura, D., Xavier, R., Sugiura, T., Chen, Y., Park, E.C., Lu, N., Selig, M., Nielsen, G., Taksir, T., Jain, R.K., et al. (1998). Tumor induction of VEGF promoter activity in stromal cells. Cell 94, 715-725. Garcia, C.K., Brown, M.S., Pathak, R.K., and Goldstein, J.L. (1995). cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. The Journal of biological chemistry 270, 1843-1849. Garcia, C.K., Goldstein, J.L., Pathak, R.K., Anderson, R.G., and Brown, M.S. (1994). Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76, 865-873. Ghosh, S., Ghosh, A., Maiti, G.P., Alam, N., Roy, A., Roychoudhury, S., and Panda, C.K. (2009). Alterations of ROBO1/DUTT1 and ROBO2 loci in early dysplastic lesions of head and neck: clinical and prognostic implications. Human genetics 125, 189-198. Grone, J., Doebler, O., Loddenkemper, C., Hotz, B., Buhr, H.J., and Bhargava, S. (2006). Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer. Oncology reports 15, 1437-1443. Halestrap, A.P. (2012). The monocarboxylate transporter family--Structure and functional characterization. IUBMB life 64, 1-9. Halestrap, A.P., and Denton, R.M. (1974). Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate. Biochemical journal 138, 313-316. Halestrap, A.P., and Price, N.T. (1999). The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochemical journal 343 Pt 2, 281-299. Hotamisligil, G.S. (2003). Inflammatory pathways and insulin action. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 27 Suppl 3, S53-55. Howitt, J.A., Clout, N.J., and Hohenester, E. (2004). Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit. The EMBO journal 23, 4406-4412. Hu, P., Margolis, B., Skolnik, E.Y., Lammers, R., Ullrich, A., and Schlessinger, J. (1992). Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors. Molecular and cellular biology 12, 981-990. Huang, S.M., Mishina, Y.M., Liu, S., Cheung, A., Stegmeier, F., Michaud, G.A., Charlat, O., Wiellette, E., Zhang, Y., Wiessner, S., et al. (2009). Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461, 614-620. Hussien, R., and Brooks, G.A. (2011). Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines. Physiological genomics 43, 255-264. Jhappan, C., Geiser, A.G., Kordon, E.C., Bagheri, D., Hennighausen, L., Roberts, A.B., Smith, G.H., and Merlino, G. (1993). Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. The EMBO journal 12, 1835-1845. Jones, C.A., London, N.R., Chen, H., Park, K.W., Sauvaget, D., Stockton, R.A., Wythe, J.D., Suh, W., Larrieu-Lahargue, F., Mukouyama, Y.S., et al. (2008). Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nature medicine 14, 448-453. Joyce, J.A., and Pollard, J.W. (2009). Microenvironmental regulation of metastasis. Nature reviews cancer 9, 239-252. Kalluri, R., and Zeisberg, M. (2006). Fibroblasts in cancer. Nature reviews cancer 6, 392-401. Kidd, T., Bland, K.S., and Goodman, C.S. (1999). Slit is the midline repellent for the robo receptor in Drosophila. Cell 96, 785-794. Kidd, T., Brose, K., Mitchell, K.J., Fetter, R.D., Tessier-Lavigne, M., Goodman, C.S., and Tear, G. (1998). Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92, 205-215. Kirat, D., Sallam, K.I., and Kato, S. (2013). Expression and cellular localization of monocarboxylate transporters (MCT2, MCT7, and MCT8) along the cattle gastrointestinal tract. Cell and tissue research 352, 585-598. Kononen, J., Bubendorf, L., Kallioniemi, A., Barlund, M., Schraml, P., Leighton, S., Torhorst, J., Mihatsch, M.J., Sauter, G., and Kallioniemi, O.P. (1998). Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nature medicine 4, 844-847. Lee, I., Lee, S.J., Kang, W.K., and Park, C. (2012). Inhibition of monocarboxylate transporter 2 induces senescence-associated mitochondrial dysfunction and suppresses progression of colorectal malignancies in vivo. Molecular cancer therapeutics 11, 2342-2351. Lin, R.Y., Vera, J.C., Chaganti, R.S., and Golde, D.W. (1998). Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. The Journal of biological chemistry 273, 28959-28965. Liotta, L.A., and Kohn, E.C. (2001). The microenvironment of the tumour-host interface. Nature 411, 375-379. Littlepage, L.E., Sternlicht, M.D., Rougier, N., Phillips, J., Gallo, E., Yu, Y., Williams, K., Brenot, A., Gordon, J.I., and Werb, Z. (2010). Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer research 70, 2224-2234. Long, H., Sabatier, C., Ma, L., Plump, A., Yuan, W., Ornitz, D.M., Tamada, A., Murakami, F., Goodman, C.S., and Tessier-Lavigne, M. (2004). Conserved roles for Slit and Robo proteins in midline commissural axon guidance. Neuron 42, 213-223. Macias, H., Moran, A., Samara, Y., Moreno, M., Compton, J.E., Harburg, G., Strickland, P., and Hinck, L. (2011). SLIT/ROBO1 signaling suppresses mammary branching morphogenesis by limiting basal cell number. Developmental cell 20, 827-840. Manabe, Y., Toda, S., Miyazaki, K., and Sugihara, H. (2003). Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions. The Journal of pathology 201, 221-228. Marlow, R., Strickland, P., Lee, J.S., Wu, X., Pebenito, M., Binnewies, M., Le, E.K., Moran, A., Macias, H., Cardiff, R.D., et al. (2008). SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. Cancer research 68, 7819-7827. Mbeunkui, F., and Johann, D.J., Jr. (2009). Cancer and the tumor microenvironment: a review of an essential relationship. Cancer chemotherapy and pharmacology 63, 571-582. Morlot, C., Thielens, N.M., Ravelli, R.B., Hemrika, W., Romijn, R.A., Gros, P., Cusack, S., and McCarthy, A.A. (2007). Structural insights into the Slit-Robo complex. Proceedings of the National Academy of Sciences of the United States of America 104, 14923-14928. Moses, L.E., Shapiro, D., and Littenberg, B. (1993). Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Statistics in medicine 12, 1293-1316. Mueller, M.M., and Fusenig, N.E. (2004). Friends or foes - bipolar effects of the tumour stroma in cancer. Nature reviews Cancer 4, 839-849. Narayan, G., Goparaju, C., Arias-Pulido, H., Kaufmann, A.M., Schneider, A., Durst, M., Mansukhani, M., Pothuri, B., and Murty, V.V. (2006). Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression. Molecular cancer 5, 16. Nguyen-Ba-Charvet, K.T., and Chedotal, A. (2002). Role of Slit proteins in the vertebrate brain. Journal of physiology 96, 91-98. Orimo, A., Gupta, P.B., Sgroi, D.C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V.J., Richardson, A.L., and Weinberg, R.A. (2005). Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121, 335-348. Park, J., Euhus, D.M., and Scherer, P.E. (2011). Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocrine reviews 32, 550-570. Pertega-Gomes, N., Vizcaino, J.R., Gouveia, C., Jeronimo, C., Henrique, R.M., Lopes, C., and Baltazar, F. (2013). Monocarboxylate transporter 2 (MCT2) as putative biomarker in prostate cancer. Prostate 73, 763-769. Pinheiro, C., Longatto-Filho, A., Scapulatempo, C., Ferreira, L., Martins, S., Pellerin, L., Rodrigues, M., Alves, V.A., Schmitt, F., and Baltazar, F. (2008). Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Archiv : an international journal of pathology 452, 139-146. Polyak, K., and Kalluri, R. (2010). The role of the microenvironment in mammary gland development and cancer. Cold Spring Harbor perspectives in biology 2, a003244. Poole, R.C., and Halestrap, A.P. (1993). Transport of lactate and other monocarboxylates across mammalian plasma membranes. The American journal of physiology 264, C761-782. Prasad, A., Paruchuri, V., Preet, A., Latif, F., and Ganju, R.K. (2008). Slit-2 induces a tumor-suppressive effect by regulating beta-catenin in breast cancer cells. The Journal of biological chemistry 283, 26624-26633. Press, O.W., Appelbaum, F., Ledbetter, J.A., Martin, P.J., Zarling, J., Kidd, P., and Thomas, E.D. (1987). Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. Blood 69, 584-591. Previdi, S., Maroni, P., Matteucci, E., Broggini, M., Bendinelli, P., and Desiderio, M.A. (2010). Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and beta-catenin/Wnt pathways. European journal of cancer 46, 1679-1691. Rich, A.R. (2007). On the frequency of occurrence of occult carcinoma of the prostrate. 1934. International journal of epidemiology 36, 274-277. Richards, R.G., Klotz, D.M., Walker, M.P., and Diaugustine, R.P. (2004). Mammary gland branching morphogenesis is diminished in mice with a deficiency of insulin-like growth factor-I (IGF-I), but not in mice with a liver-specific deletion of IGF-I. Endocrinology 145, 3106-3110. Rodemann, H.P., and Muller, G.A. (1991). Characterization of human renal fibroblasts in health and disease: II. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis. American journal of kidney diseases : the official journal of the National Kidney Foundation 17, 684-686. Rong, S., Bodescot, M., Blair, D., Dunn, J., Nakamura, T., Mizuno, K., Park, M., Chan, A., Aaronson, S., and Vande Woude, G.F. (1992). Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor. Molecular cell biology 12, 5152-5158. Rothberg, J.M., Hartley, D.A., Walther, Z., and Artavanis-Tsakonas, S. (1988). slit: an EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system. Cell 55, 1047-1059. Ruan, W., and Kleinberg, D.L. (1999). Insulin-like growth factor I is essential for terminal end bud formation and ductal morphogenesis during mammary development. Endocrinology 140, 5075-5081. Sachdev, D., and Yee, D. (2001). The IGF system and breast cancer. Endocrine-related cancer 8, 197-209. Sainsbury, J.R., Farndon, J.R., Needham, G.K., Malcolm, A.J., and Harris, A.L. (1987). Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1, 1398-1402. Samowitz, W.S., Powers, M.D., Spirio, L.N., Nollet, F., van Roy, F., and Slattery, M.L. (1999). Beta-catenin mutations are more frequent in small colorectal adenomas than in larger adenomas and invasive carcinomas. Cancer research 59, 1442-1444. Satyamoorthy, K., Li, G., Vaidya, B., Patel, D., and Herlyn, M. (2001). Insulin-like growth factor-1 induces survival and growth of biologically early melanoma cells through both the mitogen-activated protein kinase and beta-catenin pathways. Cancer research 61, 7318-7324. Schreiber, A.B., Lax, I., Yarden, Y., Eshhar, Z., and Schlessinger, J. (1981). Monoclonal antibodies against receptor for epidermal growth factor induce early and delayed effects of epidermal growth factor. Proceedings of the National Academy of Sciences of the United States of America 78, 7535-7539. Scott, A.M., Wolchok, J.D., and Old, L.J. (2012). Antibody therapy of cancer. Nature reviews Cancer 12, 278-287. Seeger, M., Tear, G., Ferres-Marco, D., and Goodman, C.S. (1993). Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron 10, 409-426. Sharma, M., Chuang, W.W., and Sun, Z. (2002). Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3beta inhibition and nuclear beta-catenin accumulation. The Journal of biological chemistry 277, 30935-30941. Silberstein, G.B., and Daniel, C.W. (1987). Reversible inhibition of mammary gland growth by transforming growth factor-beta. Science 237, 291-293. Simian, M., Hirai, Y., Navre, M., Werb, Z., Lochter, A., and Bissell, M.J. (2001). The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development 128, 3117-3131. Sternlicht, M.D., Sunnarborg, S.W., Kouros-Mehr, H., Yu, Y., Lee, D.C., and Werb, Z. (2005). Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin. Development 132, 3923-3933. Sun, M., Paciga, J.E., Feldman, R.I., Yuan, Z., Coppola, D., Lu, Y.Y., Shelley, S.A., Nicosia, S.V., and Cheng, J.Q. (2001). Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer research 61, 5985-5991. Sundaresan, V., Chung, G., Heppell-Parton, A., Xiong, J., Grundy, C., Roberts, I., James, L., Cahn, A., Bench, A., Douglas, J., et al. (1998). Homozygous deletions at 3p12 in breast and lung cancer. Oncogene 17, 1723-1729. Tessier-Lavigne, M., and Goodman, C.S. (1996). The molecular biology of axon guidance. Science 274, 1123-1133. Torti, F.M., Torti, S.V., Larrick, J.W., and Ringold, G.M. (1989). Modulation of adipocyte differentiation by tumor necrosis factor and transforming growth factor beta. The Journal of cell biology 108, 1105-1113. Tseng, R.C., Lee, S.H., Hsu, H.S., Chen, B.H., Tsai, W.C., Tzao, C., and Wang, Y.C. SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis. Cancer research 70, 543-551. Tseng, R.C., Lee, S.H., Hsu, H.S., Chen, B.H., Tsai, W.C., Tzao, C., and Wang, Y.C. (2010). SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis. Cancer research 70, 543-551. Tyan, S.W., Kuo, W.H., Huang, C.K., Pan, C.C., Shew, J.Y., Chang, K.J., Lee, E.Y., and Lee, W.H. (2011). Breast cancer cells induce cancer-associated fibroblasts to secrete hepatocyte growth factor to enhance breast tumorigenesis. PLoS one 6, e15313. van de Vijver, M.J., He, Y.D., van't Veer, L.J., Dai, H., Hart, A.A., Voskuil, D.W., Schreiber, G.J., Peterse, J.L., Roberts, C., Marton, M.J., et al. (2002). A gene-expression signature as a predictor of survival in breast cancer. The New England Journal of medicine 347, 1999-2009. Wang, K.H., Brose, K., Arnott, D., Kidd, T., Goodman, C.S., Henzel, W., and Tessier-Lavigne, M. (1999). Biochemical purification of a mammalian slit protein as a positive regulator of sensory axon elongation and branching. Cell 96, 771-784. Wilson, M.C., Kraus, M., Marzban, H., Sarna, J.R., Wang, Y., Hawkes, R., Halestrap, A.P., and Beesley, P.W. (2013). The neuroplastin adhesion molecules are accessory proteins that chaperone the monocarboxylate transporter MCT2 to the neuronal cell surface. PloS one 8, e78654. Wiseman, B.S., and Werb, Z. (2002). Stromal effects on mammary gland development and breast cancer. Science 296, 1046-1049. Wong, K., Ren, X.R., Huang, Y.Z., Xie, Y., Liu, G., Saito, H., Tang, H., Wen, L., Brady-Kalnay, S.M., Mei, L., et al. (2001). Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell 107, 209-221. Zallen, J.A., Yi, B.A., and Bargmann, C.I. (1998). The conserved immunoglobulin superfamily member SAX-3/Robo directs multiple aspects of axon guidance in C. elegans. Cell 92, 217-227. Ahima, R.S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., and Flier, J.S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature 382, 250-252. Alajez, N.M., Lenarduzzi, M., Ito, E., Hui, A.B., Shi, W., Bruce, J., Yue, S., Huang, S.H., Xu, W., Waldron, J., et al. (2011). MiR-218 suppresses nasopharyngeal cancer progression through downregulation of survivin and the SLIT2-ROBO1 pathway. Cancer research 71, 2381-2391. Bachelot, T., Ray-Coquard, I., Menetrier-Caux, C., Rastkha, M., Duc, A., and Blay, J.Y. (2003). Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. British journal of cancer 88, 1721-1726. Barbareschi, M., Pelosio, P., Caffo, O., Buttitta, F., Pellegrini, S., Barbazza, R., Dalla Palma, P., Bevilacqua, G., and Marchetti, A. (1997). Cyclin-D1-gene amplification and expression in breast carcinoma: relation with clinicopathologic characteristics and with retinoblastoma gene product, p53 and p21WAF1 immunohistochemical expression. International journal of cancer Journal international du cancer 74, 171-174. Bashaw, G.J., Kidd, T., Murray, D., Pawson, T., and Goodman, C.S. (2000). Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor. Cell 101, 703-715. Berg, A.H., Combs, T.P., Du, X., Brownlee, M., and Scherer, P.E. (2001). The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nature medicine 7, 947-953. Bhowmick, N.A., Neilson, E.G., and Moses, H.L. (2004). Stromal fibroblasts in cancer initiation and progression. Nature 432, 332-337. Bissell, M.J., and Hines, W.C. (2011). Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nature medicine 17, 320-329. Brantley-Sieders, D.M., Dunaway, C.M., Rao, M., Short, S., Hwang, Y., Gao, Y., Li, D., Jiang, A., Shyr, Y., Wu, J.Y., et al. (2011). Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium. Cancer research 71, 976-987. Broer, S., Broer, A., Schneider, H.P., Stegen, C., Halestrap, A.P., and Deitmer, J.W. (1999). Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochemical journal. 341 ( Pt 3), 529-535. Brose, K., Bland, K.S., Wang, K.H., Arnott, D., Henzel, W., Goodman, C.S., Tessier-Lavigne, M., and Kidd, T. (1999). Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96, 795-806. Brown, L.F., Guidi, A.J., Schnitt, S.J., Van De Water, L., Iruela-Arispe, M.L., Yeo, T.K., Tognazzi, K., and Dvorak, H.F. (1999). Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clininal cancer research 5, 1041-1056. Brunn, G.J., Williams, J., Sabers, C., Wiederrecht, G., Lawrence, J.C., Jr., and Abraham, R.T. (1996). Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. The EMBO journal 15, 5256-5267. Cantley, L.C., and Neel, B.G. (1999). New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proceedings of the National Academy of Sciences of the United States of America 96, 4240-4245. Dallol, A., Forgacs, E., Martinez, A., Sekido, Y., Walker, R., Kishida, T., Rabbitts, P., Maher, E.R., Minna, J.D., and Latif, F. (2002). Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers. Oncogene 21, 3020-3028. Dallol, A., Morton, D., Maher, E.R., and Latif, F. (2003). SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells. Cancer research 63, 1054-1058. Daniel, C.W., Robinson, S., and Silberstein, G.B. (1996). The role of TGF-beta in patterning and growth of the mammary ductal tree. J Mammary Gland Biol Neoplasia 1, 331-341. Dickson, B.J., and Gilestro, G.F. (2006). Regulation of commissural axon pathfinding by slit and its Robo receptors. Annual review of cell and developmental biology 22, 651-675. Dieudonne, M.N., Machinal-Quelin, F., Serazin-Leroy, V., Leneveu, M.C., Pecquery, R., and Giudicelli, Y. (2002). Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun 293, 622-628. Dirat, B., Bochet, L., Dabek, M., Daviaud, D., Dauvillier, S., Majed, B., Wang, Y.Y., Meulle, A., Salles, B., Le Gonidec, S., et al. (2011). Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer research 71, 2455-2465. Elliott, B.E., Tam, S.P., Dexter, D., and Chen, Z.Q. (1992). Capacity of adipose tissue to promote growth and metastasis of a murine mammary carcinoma: effect of estrogen and progesterone. International journal of cancer 51, 416-424. Fan, X., Labrador, J.P., Hing, H., and Bashaw, G.J. (2003). Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline. Neuron 40, 113-127. Finak, G., Bertos, N., Pepin, F., Sadekova, S., Souleimanova, M., Zhao, H., Chen, H., Omeroglu, G., Meterissian, S., Omeroglu, A., et al. (2008). Stromal gene expression predicts clinical outcome in breast cancer. Nature medicine 14, 518-527. Fry, M.J. (2001). Phosphoinositide 3-kinase signalling in breast cancer: how big a role might it play? Breast cancer research : BCR 3, 304-312. Fukumura, D., Xavier, R., Sugiura, T., Chen, Y., Park, E.C., Lu, N., Selig, M., Nielsen, G., Taksir, T., Jain, R.K., et al. (1998). Tumor induction of VEGF promoter activity in stromal cells. Cell 94, 715-725. Garcia, C.K., Brown, M.S., Pathak, R.K., and Goldstein, J.L. (1995). cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1. The Journal of biological chemistry 270, 1843-1849. Garcia, C.K., Goldstein, J.L., Pathak, R.K., Anderson, R.G., and Brown, M.S. (1994). Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76, 865-873. Ghosh, S., Ghosh, A., Maiti, G.P., Alam, N., Roy, A., Roychoudhury, S., and Panda, C.K. (2009). Alterations of ROBO1/DUTT1 and ROBO2 loci in early dysplastic lesions of head and neck: clinical and prognostic implications. Human genetics 125, 189-198. Grone, J., Doebler, O., Loddenkemper, C., Hotz, B., Buhr, H.J., and Bhargava, S. (2006). Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer. Oncology reports 15, 1437-1443. Halestrap, A.P. (2012). The monocarboxylate transporter family--Structure and functional characterization. IUBMB life 64, 1-9. Halestrap, A.P., and Denton, R.M. (1974). Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate. Biochemical journal 138, 313-316. Halestrap, A.P., and Price, N.T. (1999). The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochemical journal 343 Pt 2, 281-299. Hotamisligil, G.S. (2003). Inflammatory pathways and insulin action. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 27 Suppl 3, S53-55. Howitt, J.A., Clout, N.J., and Hohenester, E. (2004). Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit. The EMBO journal 23, 4406-4412. Hu, P., Margolis, B., Skolnik, E.Y., Lammers, R., Ullrich, A., and Schlessinger, J. (1992). Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors. Molecular and cellular biology 12, 981-990. Huang, S.M., Mishina, Y.M., Liu, S., Cheung, A., Stegmeier, F., Michaud, G.A., Charlat, O., Wiellette, E., Zhang, Y., Wiessner, S., et al. (2009). Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461, 614-620. Hussien, R., and Brooks, G.A. (2011). Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines. Physiological genomics 43, 255-264. Jhappan, C., Geiser, A.G., Kordon, E.C., Bagheri, D., Hennighausen, L., Roberts, A.B., Smith, G.H., and Merlino, G. (1993). Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. The EMBO journal 12, 1835-1845. Jones, C.A., London, N.R., Chen, H., Park, K.W., Sauvaget, D., Stockton, R.A., Wythe, J.D., Suh, W., Larrieu-Lahargue, F., Mukouyama, Y.S., et al. (2008). Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nature medicine 14, 448-453. Joyce, J.A., and Pollard, J.W. (2009). Microenvironmental regulation of metastasis. Nature reviews cancer 9, 239-252. Kalluri, R., and Zeisberg, M. (2006). Fibroblasts in cancer. Nature reviews cancer 6, 392-401. Kidd, T., Bland, K.S., and Goodman, C.S. (1999). Slit is the midline repellent for the robo receptor in Drosophila. Cell 96, 785-794. Kidd, T., Brose, K., Mitchell, K.J., Fetter, R.D., Tessier-Lavigne, M., Goodman, C.S., and Tear, G. (1998). Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92, 205-215. Kirat, D., Sallam, K.I., and Kato, S. (2013). Expression and cellular localization of monocarboxylate transporters (MCT2, MCT7, a | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57253 | - |
| dc.description.abstract | 在腫瘤發生過程中，除了癌細胞本身的生長調控之外，周圍環境因子扮演著相當重要的角色。乳房組織中，纖維母細胞（fibroblast）和脂肪細胞（adipocyte）是主要構成乳房的周圍細胞。正常乳腺發育過程中，上皮細胞（epithelial cell）和這些周圍細胞之間的交互作用是受到複雜而且嚴謹的控制。當細胞之間的調控失去控制時，則容易造成細胞的異常增殖導致癌症的發生。因此，研究這些細胞之間的調控對於腫瘤發生學是相當重要的課題。
本論文分別探討纖維母細胞和脂肪細胞對於癌細胞的影響。先前的研究發現，纖維母細胞會促進乳癌細胞生長。然而在實驗裡發現，並非所有的乳癌細胞都會被纖維母細胞所促進生長。纖維母細胞對於乳癌細胞的反應可以分成兩群，一群是會被纖維母細胞所促進生長，而在另一群乳癌細胞中，纖維母細胞反而會抑制生長。進一步的研究指出，這類會受抑制的乳癌細胞表面會表現ROBO1的膜蛋白，透過纖維母細胞釋放SLIT2來抑制癌細胞的生長。當SLIT2/ROBO1被活化後，細胞內的訊息傳導（PI3K/AKT）會被阻斷，造成β-catenin無法轉移到細胞核，進而抑制cyclin D1和c-myc的表現。在臨床檢體上，乳癌細胞中有ROBO1高表現的病人擁有比較好的預後，然而纖維母細胞中SLIT2低表現的則容易有淋巴結轉移。 在另一部分脂肪細胞的研究中，我的實驗證實脂肪細胞會促進具有表現MCT2膜蛋白的乳癌細胞生長。同樣在臨床檢體也證實，高表現MCT2的病人會有比較差的預後。 綜合以上的結果，我的實驗對於乳癌細胞與微環境細胞的交互作用，提出了新的訊息傳遞途徑，藉由了解這些訊息傳導途徑，將有助於發展出有效的癌症治療藥物。 | zh_TW |
| dc.description.abstract | The tumor microenvironment plays a critical role in regulating cancer progression. In breast, stromal fibroblasts and adipocytes are two major components of the microenvironment. Their roles in breast tumor formation are complex. Stromal cells can promote tumor growth through paracrine factors; however, restraint of malignant carcinoma progression by the microenvironment has also been observed. The mechanisms that underlie this paradox have remained unclear. We found that the tumorigenic potential of breast cancer cells can be determined by an interaction between ROBO1 receptors in cancer cells and its ligand SLIT2 secreted from stromal fibroblasts. The presence of an active SLIT2/ROBO1 signal blocked the translocation of β-catenin into nucleus, leading to down-regulation of c-myc and cyclin D1 via the PI3K pathway. Clinically, high ROBO1 expression in breast cancer cells was correlated with better prognosis, whereas low SLIT2 expression in the stromal fibroblasts was associated with lymph node metastasis. This clinical correlation further demonstrated the significance of the interaction between breast cancer cells and surrounding fibroblasts in suppression of tumorigenesis. In contrast to fibroblast-mediated suppression, adipocytes have been shown to promote breast tumor progression. We found that MCT2 expressed in breast cancer cells played a key role in adipocyte-mediated tumorigenesis. MCT2, a monocarboxylate transporter, enhanced tumor growth in response to adipocyte-secreted | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T06:39:20Z (GMT). No. of bitstreams: 1 ntu-103-D98442005-1.pdf: 5661423 bytes, checksum: 98d2d5731978bac9f8ecff40c321a416 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 中文摘要……………………………………………………………………………………..…iii
Abstract……………………………………………………………………………………...…...iv Chapter I - Overview Part I - Mammary gland development…………………………………………..…………..2 Part II - Tumor microenvironment………………………………………………….……..…4 Part III - Fibroblast…..………………………………………………………………….……..5 Part IV - Adipocyte…………………………………………………………………….….…....6 Part V - Robo1…………………………………………………………………………….…...7 Part VI - Slit2……………………………………………………………………………..........9 Part VII - MCT2………………………………………………………………….……….….10 Chaper II- Activation of ROBO1 signaling of breast cancer cells by SLIT2 from stromal fibroblast restrains tumorigenesis via blocking PI3K/Akt/β-catenin pathway Introducion………………………………………………………………………………….....14 Materials and Methods…………………………………………………………………...…...16 Results…………………………………………………………………………………..……...20 Discussion.………………………………………………………….…………………….…....26 List of Tables…………………………………………………………………………..……....29 List of Figures……………………………………………………………………..…………..35 Chaper III- Adipocytes promote breast cancer growth through MCT2 transporter Introducion…………………………………..…………………………………………….…..48 Materials and Methods...…………………………..………………………………………….50 Results………………………………………………………………………………………….54 Discussion….…………………………………………………………………………………..57 List of Tables…………………………………………………………………………………..59 List of Figures…………………………………………………………………………………62 Chaper IV- Conclusions and future directions Conclusions…………………………………………………………………………………….73 Future directions……………………...……………………………………………………….74 List of Figures…………………..…………………………………………...…………………76 References……………………………………………………………………………………….77 | |
| dc.language.iso | en | |
| dc.subject | 乳癌 | zh_TW |
| dc.subject | 周圍細胞 | zh_TW |
| dc.subject | 癌症 | zh_TW |
| dc.subject | 脂肪細胞 | zh_TW |
| dc.subject | 纖維母細胞 | zh_TW |
| dc.subject | robo1 | en |
| dc.subject | breast cancer | en |
| dc.subject | microenvironemt | en |
| dc.subject | fibroblast | en |
| dc.subject | adipocyte | en |
| dc.subject | mct2 | en |
| dc.title | 乳癌細胞與其微環境交互作用之探討 | zh_TW |
| dc.title | Microenvironment and tumorigenesis: interplay between breast cancer cell and its microenvironment | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 李文華 | |
| dc.contributor.oralexamcommittee | 林敬哲,翁芬華,張明富,李明學,余明俊 | |
| dc.subject.keyword | 癌症,周圍細胞,乳癌,纖維母細胞,脂肪細胞, | zh_TW |
| dc.subject.keyword | breast cancer,microenvironemt,fibroblast,adipocyte,robo1,mct2, | en |
| dc.relation.page | 89 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-07-30 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-103-1.pdf 未授權公開取用 | 5.53 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。