Grb7在乳腺發育暨癌症發展中所扮演的角色

Abstract

Growth factor receptor-bound protein 7 (Grb7)為一個在癌症發展中扮演重要的角色的銜接蛋白。Grb7參與有關癌細胞增生，侵入以及存活傳遞路徑的調控。ErbB2在乳癌中是一個最主要的致癌基因，由於在人類以及小鼠的基因體上Grb7基因的位置臨近於ErbB2，因此很大一部分有關Grb7的文獻都集中在乳癌相關的研究。先前的研究顯示Grb7 knockdown可大量抑制SK-BR3的生長、移動以及腫瘤生長的能力。正常的乳腺發育與乳腺癌發展有著非常類似的特性，在本研究裡，我們研究Grb7在乳腺發育中伴演的角色。我們成功地利用CRISPR-Cas9技術將C57BL/6小鼠的Grb7剔除，我們發現剔除Grb7可以促進乳腺管道的分枝並且延遲乳腺退化。此外，本研究也利用了B16-F10的皮下腫瘤和肺轉移的模型來探討腫瘤微環境中的Grb7對癌症發展的影響。從活體實驗的結果得知，Grb7 剔除大大地影響了B16-F10轉移到肺部的效率。希望本研究的結果將能更清楚了解Grb7在生物體內的作用，並將進一步促進對抗癌症的藥物開發。 關鍵詞: Growth factor receptor-bound protein (Grb7)； 乳腺發育； 癌症發展； 肺轉

Growth factor receptor-bound protein 7 (Grb7) is an adaptor protein that regulates tumor progression by integrating several important pathways for cell proliferation, invasion and survival. The role of Grb7 was intensively studied in breast cancer, since it is closely related to the oncogene ERBB2. Prior study from out lab has also indicated that knockdown the expression of Grb7 ablates the proliferation, migration and tumorigenesis of the SK-BR3 cell line in vitro. Since the normal development of mammary gland shares similar characteristics with the mammary gland tumorigenesis, we questioned whether Grb7 participates in the development of the normal mammary gland. Using CRISPR-Cas9 generated Grb7 knockout C57BL/6 mice, we have investigated the role of Grb7 in normal mammary gland development in vivo. According to our study, Grb7 knockout has slightly promote branching and delayed involution. Also, we applied the B16-F10 subcutaneous and lung metastasis models to see investigate the influence of Grb7 knockout on tumor progression. Grb7 knockout has affected the tumor colonization on lungs during metastasis. The results from this study will better illustrate the in vivo role of Grb7, which will further contribute to the drug development against cancers. Keywords: Growth factor receptor-bound protein (Grb7); mammary gland development; tumor growth; lung metastasis