Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS
Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS
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DOI：
10.1096/fj.06-7799com
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发表时间：
2007-07-01
期刊：
影响因子：
4.8
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Liang, Jie;Pan, Yanglin;Fan, Daiming
细胞朊蛋白（Cellular Prion Protein，PrPC）是朊病毒疾病发病和传播的关键蛋白，其功能至今仍不清楚。PrPC的假定作用被认为与细胞信号传导、存活和分化有关。在先前的研究中，我们发现PrPC在胃癌组织中过表达。在本报告中，我们表明，PrPC的异位表达可以促进胃癌细胞的肿瘤发生，增殖和G1/S转换。此外，CyclinD 1，一个与细胞周期相关的蛋白质，被证明是显着上调PrPC在mRNA和蛋白质水平。PI 3 K/Akt信号通路介导了PrPC信号，PrPC可增加磷酸化Akt的表达，Akt的特异性抑制剂LY 294002可显著抑制PrPC诱导的SGC 7901细胞生长和CyclinD 1的反式激活。八肽重复区在这一功能中起着至关重要的作用，因为该区域的缺失消除或减少了这些作用。本研究表明，PrPC过表达可能通过激活PI 3 K/ Akt信号通路，进而激活CyclinD 1的转录，调控G1/S期转换，从而促进胃癌细胞的发生和增殖，其中八肽重复区可能是不可或缺的区域。梁杰，潘，Y.，Zhang，D.，中国农业科学院农业研究所所长，Guo，C.，中国农业科学院，施，Y.，王杰，陈玉，王，X.，刘杰，郭，X.，陈志，乔，T.，范，D.细胞朊蛋白促进人胃癌细胞SGC 7901和AGS增殖及G1/S转换
The function of cellular prion protein ( PrPC), the essential protein for the pathogenesis and transmission of prion diseases, is still largely unknown. The putative roles of PrPC are thought to be related to cell signaling, survival, and differentiation. In a previous study, we showed that PrPC was overexpressed in gastric cancer tissues. In the present report, we show that ectopic expression of PrPC could promote tumorigenesis, proliferation, and G1/S transition in gastric cancer cells. Furthermore, CyclinD1, a protein related to cell cycle, was shown to be significantly up-regulated by PrPC at both mRNA and protein levels. PI3K/Akt pathway mediated above PrPC signal since PrPC increased the expression of phosphorylated Akt, and the specific inhibitor of Akt, LY294002, could markedly suppress growth of SGC7901 and transactivation of CyclinD1 induced by PrPC. Octapeptide repeat region played a vital role in this function, as deletion of this region abolished or reduced these effects. Collectively, this study demonstrates that overexpression of PrPC might promote the tumorigenesis and proliferation of gastric cancer cells at least partially through activation of PI3K/ Akt pathway and subsequent transcriptional activation of CyclinD1 to regulate the G1/S phase transition, in which octapeptide repeat region might be an indispensable region.-Liang, J., Pan, Y., Zhang, D., Guo, C., Shi, Y., Wang, J., Chen, Y., Wang, X., Liu, J., Guo, X., Chen, Z., Qiao, T., Fan, D. Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS.