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標題: | PartⅠ: 探討Annexin A7對癌細胞轉移的影響;PartⅡ: Neuregulin在神經細胞促進Interleukin-10釋放之作用 PartⅠ: Role of Annexin A7 in the cell migration of cancer cells ; PartⅡ: Regulation of Interleukin-10 expression by neuregulin-1 in neurons |
作者: | Wan-Jung Tsai 蔡宛蓉 |
指導教授: | 符文美 |
關鍵字: | annexin A7,細胞轉移,人類膠細胞瘤,老鼠乳腺癌,NRG1,介白質-10,人類神經母細胞細胞株SH-SY5Y,初級大腦皮質神經細胞, annexin A7,cell migration,human glioma cell,mouse mammary cell,NRG1,Interleukin-10,SH-SY5Y,primary cortex neuronal culture, |
出版年 : | 2009 |
學位: | 碩士 |
摘要: | Part Ⅰ: Role of Annexin A7 in the cell migration of cancer cells
Approximately 90% of cancer death arises from the metastatic spread of primary tumors. Cell migration is one of the key steps in tumor spreading. Therefore, the identification of molecules and characterization of the mechanisms regulating cell migration is essential to understand metastasis development. Annexin A7, as a Ca2+-binding protein, has been implicated in the regulation of intracellular calcium homeostasis in several cell types and species. Annexin A7 has recently been associated with tumor metastasis in many different tumor types. We reported here that knock down of annexin A7 expression by shRNA increased the cell migration of both U251 human giloma cells and 4T1 mouse mammary cells. In addition, the increase of cell migration could be reversed by treatment with a pharmacological inhibitor of store-operated calcium channels. On the other hand, we found that the loss of annexin A7 altered the phosphorylation levels of Akt, with increased pAkt in U251 annexin-A7 knockdown stable clone and decreased pAkt in 4T1 annexin-A7 knockdown stable pool. Treatment with PI3 kinase inhibitor (LY294002) decreased the cell migration of U251 annexin-A7 knockdown stable clone; however, it did not affect the cell migration of 4T1 annexin-A7 kmockdown stable pool. Our data demonstrate a role for annexin A7 in cell migration and suggest that intracellular Ca2+ levels and phosphorylation of Akt may be involved in the mechanism of the increase of cell migration by knock down of annexin A7. Part Ⅱ : Regulation of Interleukin-10 expression by neuregulin-1 in neurons Schizophrenia is a severe and highly debilitating mental disorder in which multiple genes and environmental factors interact to cause the schizophrenia phenotype. Neuregulin-1 (NRG1) is one of the candidate genes which is identified in a genome-wide scan of schizophrenia families performed in Iceland in 2002. Here we found that NRG +/- mutant mice expressed less Interleukin-10 mRNA and exogenous application of NRG1 increased IL-10 mRNA expression in SH-SY5Y human neuroblastoma cells. The erbB-specific inhibitor PD158780 decreased NRG1-induced IL-10 mRNA expression. Pharmacological inhibition of ERK activation also inhibited NRG1-induced IL-10 mRNA expression. On the other hand, we found that exogenous application of IL-10 increased the number of primary dendrite, cover area, total dendritic length, and branching in cultured cortex neurons at Day2. IL-10 dose-dependently increased synapsin protein expression in cultured cortex neurons at Day 6-7. Our results suggest that IL-10 mRNA expression induced by NRG1 in SH-SY5Y cells requires erbB tyrosine kinases and pERK singnaling networks. In addition, our results suggest that IL-10 may play a role in neurite outgrowth and synaptogenesis. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43080 |
全文授權: | 有償授權 |
顯示於系所單位: | 藥理學科所 |
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