Bao S, Chang M S, Auclair D, Sun Y, Wang Y, Wong W K, Zhang J, Liu Y, Qian X, Sutherland R, Magi-Galluzi C, Weisberg E, Cheng E Y, Hao L, Sasaki H, Campbell M S, Kraeft S K, Loda M, Lo K M, Chen L B
Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Res. 1999 May 1;59(9):2023-8.
Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anticancer drugs.
利用回文PCR - cDNA展示法,我们克隆了一个相对于正常结肠而言在人结肠癌中过表达的新基因。在所检测的正常组织中,只有睾丸高水平表达该基因。序列分析显示它与粟酒裂殖酵母的检查点基因rad17和酿酒酵母的RAD24具有广泛的同源性。这个被命名为hRad17的新基因定位于5q12,13.1染色体区域,该区域在多种人类癌症中已知会发生缺失。已鉴定出hRad17的启动子区域和一个假基因。人结肠癌中hRad17表达的增加可能与这些细胞在治疗期间对DNA损伤剂的已知抗性有关,而多种癌症中hRad17的缺失可能使它们更容易发生突变率增加以及对包括辐射和抗癌药物在内的DNA损伤剂敏感性增强。