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Hiwi基因在人胃癌中的表达与癌细胞增殖相关。

Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells.

作者信息

Liu Xiaoying, Sun Yu, Guo Jianping, Ma Hong, Li Jiyou, Dong Bin, Jin Genglin, Zhang Jianzhi, Wu Jian, Meng Lin, Shou Chengchao

机构信息

Department of Biochemistry and Molecular Biology, Peking University School of Oncology, Beijing Institute for Cancer Research, Beijing, People's Republic of China.

出版信息

Int J Cancer. 2006 Apr 15;118(8):1922-9. doi: 10.1002/ijc.21575.

Abstract

Stem cell genetics research may be critical to our understanding of carcinogenesis, as both stem cells and cancer cells possess the ability to self-renew. Recent discoveries have indicated that the piwi family of genes plays an essential role in stem cell self-renewal in diverse organisms. The hiwi gene, the human homolog of the piwi family, participates in germ cell proliferation and its overexpression may cause the development of germ cell malignancy, but its expression and function in epithelial solid cancers have not been explored. In the present study, we investigated whether there was an association between hiwi expression and human gastric cancer and its potential mechanism. RT-PCR findings demonstrated that hiwi was expressed in different gastric cancer cell lines. To identify the HIWI protein in gastric cancer, we developed a specific monoclonal antibody against HIWI and immunohistochemistry was performed on various gastric tissues. We found that the expression ratio of hiwi in normal gastric tissues, atrophic gastritis, intestinal metaplasia and gastric cancers was 10% (5/50), 36% (18/50), 36% (18/50) and 76% (38/50), respectively, which was consistent with precancerous development. Notably, the expression pattern of hiwi in gastric cancer tissues was similar to that of Ki67, which was used as a marker of proliferation. Moreover, the suppression of hiwi by antisense or RNAi inhibited the growth of gastric cancer cells and induced cell cycle arrest in G2/M phase. These results suggest that hiwi may be involved in the development of gastric cancer and is a potential target for cancer therapy.

摘要

干细胞遗传学研究对于我们理解癌症发生可能至关重要,因为干细胞和癌细胞都具有自我更新的能力。最近的发现表明,piwi基因家族在多种生物体的干细胞自我更新中起着至关重要的作用。hiwi基因是piwi家族的人类同源物,参与生殖细胞增殖,其过表达可能导致生殖细胞恶性肿瘤的发生,但其在上皮性实体癌中的表达和功能尚未得到探索。在本研究中,我们调查了hiwi表达与人类胃癌之间是否存在关联及其潜在机制。逆转录聚合酶链反应(RT-PCR)结果表明,hiwi在不同的胃癌细胞系中表达。为了在胃癌中鉴定HIWI蛋白,我们开发了一种针对HIWI的特异性单克隆抗体,并对各种胃组织进行了免疫组织化学检测。我们发现,hiwi在正常胃组织、萎缩性胃炎、肠化生和胃癌中的表达率分别为10%(5/50)、36%(18/50)、36%(18/50)和76%(38/50),这与癌前病变的发展一致。值得注意的是,hiwi在胃癌组织中的表达模式与用作增殖标志物的Ki67相似。此外,反义或RNA干扰抑制hiwi可抑制胃癌细胞的生长并诱导细胞周期停滞在G2/M期。这些结果表明,hiwi可能参与胃癌的发生发展,是癌症治疗的一个潜在靶点。

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