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標題: 探討GCIP在癌症細胞中的調控機制
Investigation of regulation mechanism of GCIP in cancer cell
作者: 黃琳倫
Lin-Lun Huang
關鍵字: 癌症;GCIP;MEK2;c-Myc;ITGAV;cancer;GCIP;MEK2;c-Myc;ITGAV
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GCIP (Grap2 and CyclinD1 interacting protein)是一個helix-loop-helix leucine zipper蛋白質,但是缺乏基本的DNA結合區域,在過去文獻指出GCIP是一個抑癌蛋白,不論在體外或體內的實驗中可以抑制癌細胞生長、增殖以及轉移。在我們先前實驗發現,GCIP和MEK2 (Mitogen-activated protein kinase kinase 2)會直接互相作用,我們的數據中再次證實MEK2會使GCIP的蛋白穩定度下降,MEK2也會磷酸化GCIP在serine上。
  在過去文獻指出GCIP會抑制癌細胞的轉移,而我們先前實驗發現GCIP抑制轉移並不是透過epithelial-mesenchymal transition (EMT),也不是透過轉移相關基因,如Rac1、Rho A,而GCIP蛋白可以負調控ITGAV (Integrin αv) 基因的表現,因此,我們利用luciferase assay觀察到GCIP和c-Myc會共同負調控ITGAV的轉錄,這些研究結果可以提供GCIP可以抑制癌細胞生長及轉移,有助於設計新的癌症治療策略來治療癌細胞。

GCIP (Grap2 and CyclinD1 interacting protein) is a helix-loop-helix leucine zipper protein without DNA-binding domain. Recent studies had been demonstrated that GCIP is a tumor suppressor that suppress cell growth, proliferation, migration in vitro and in vivo. In our previous studies, it suggested GCIP and MEK2 (Mitogen-activated protein kinase kinase 2) will interact directly. Our data also confirmed MEK2 would reduce the protein stability of GCIP and phosphorylate GCIP on serine site.
GCIP was reported the ability of inhibition of cancer cell metastasis. Based on that, our past research demonstrated GCIP-mediated metastatic inhibition is through neither epithelial - mesenchymal transition (EMT) nor the metastasis related genes, such as Rac1, Rho A. Importantly, GCIP protein can regulate ITGAV (Integrin αv) gene expression negatively. Therefore, we used the luciferase assay observed GCIP and c-Myc will jointly mediate the transcription of ITGAV on negative regulation. These results indicate GCIP can inhibit the growth and metastasis of cancer cells, and it can be designed as a new cancer treatment strategy of cancers.
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