肿瘤抑制基因ARHI的生物学功能及研究进展

肿瘤是一种基因病,抑癌基因在抵御肿瘤发生、发展中起着重要作用。ARHI(aplysia ras hom olog I)/NOEY2 是一个新发现的抑癌基因,是 ras/rap超家族成员之一,与 ras家族有50%~60%的同源性,位于人染色体1p31,属小GTP结合蛋白,是该家族第1个被报道的肿瘤抑制基因。ARHI基因编码的蛋白在人类多种组织表达,其中正常卵巢的ARHI表达最高。ARHI是一个印迹基因,印迹机制可能与其CpG岛的差异甲基化有关。ARHI 参与细胞周期调控可能作用于cyclin D1 ,使其不能与 CDK结合形成活性激酶,从而使细胞停止于 G1 期。AR HI可能通过依赖caspase和 calpain两条途径参与信号通路传导诱发细胞凋亡。该基因的异常表达跟多种肿瘤的发生、发展有关。ARHI基因参与了乳腺癌的发生和发展,该基因的表达缺失可能与乳腺癌的转移机制有关。卵巢癌、乳腺癌存在广泛的1p31缺失,其中 ARHI 基因是最常见的一个缺失区域。ARHI基因和蛋白在胰腺癌组织中有较高比例的缺失,提示该基因和蛋白在胰腺癌的发生中起一定作用。ARHI基因在膀胱癌、肝癌、前列腺癌等其他肿瘤中也有不同程度的表达异常。

Biological function and research progress of tumor suppressor gene ARHI

Tumor is a kind of genic disease. Tumor suppressor gene has important effects on resisting the tumor. ARHI/NOEY2 is a new tumor suppressor imprinted gene. It is a member of ras/rap super family, which has 50%-60%homology with ras family and locates in 1p31 on human chromosome. Belonging to small GTP binding protein, it is the first reported tumor suppressor gene of ras family. The ARHI gene encodes protein that expresses widely in most kinds of human tissues. ARHI is an imprinted gene; its imprinting mechanism may be related with differencing methylation in CpG sites. Effecting on cyclin D1, ARHI negatively involves in the regulation of cell cycle and blocks the cell growth at G1 period. ARHI can induce the cell apoptosis through the caspase and calpain cell signal transduction pathway. The abnormal expression of ARHI is closely correlative with the onset of tumor. It is reported that the ovary cancer and breast cancer has wildly 1p31 deletionsin,in which ARHI is the most common region. The deletion of ARHI happens rather often in pancreas cancer. Moreover, it also expresses abnormally in bladder cancer, liver cancer, prostate cancer and etc to some extent.