Loss of Betaig-h3 protein is frequent in primary lung carcinoma and related to tumorigenic phenotype in lung cancer cells
Loss of Betaig-h3 protein is frequent in primary lung carcinoma and related to tumorigenic phenotype in lung cancer cells
复制标题
DOI：
10.1002/mc.20167
复制
发表时间：
2006-02-01
影响因子：
4.6
通讯作者：
Hei, TK
中科院分区：
文献类型：
--
作者：
Zhao, YL;El-Gabry, M;Hei, TK
β ig-h3作为转化生长因子-P诱导的分泌蛋白，已被认为调节细胞粘附和肿瘤形成。尽管我们之前已经证明Betaig-h3基因的下调参与了辐射诱导的人支气管上皮细胞的细胞转化，但其在原发性人肺癌中的调节尚不清楚。在这项研究中，Betaig-h3的表达在130原发性肺癌免疫组化研究。在130例原发性肺癌中，45例β-h3蛋白相对于正常肺组织缺失或减少2倍以上。在缺乏内源性Betaig-h3蛋白的H522肺癌细胞中恢复Betaig-h3表达显著抑制其体外细胞生长和体内致瘤性。此外，与正常人支气管上皮细胞相比，亲代H522癌细胞对依托泊苷诱导的凋亡具有抗性。然而，H522癌细胞中Betaig-h3表达的恢复导致对凋亡诱导的敏感性显著高于亲本肿瘤细胞。IGFBP 3在转染Betaig-h3的H522细胞中表达上调，可能介导Betaig-h3基因的凋亡敏感性和抗肿瘤功能。这些观察结果表明，Betaig-h3基因的下调是一个常见的事件，并与人类肺癌的肿瘤进展。(c)2005 Wiley-Liss，Inc.
Betaig-h3 as a secreted protein induced by transforming growth factor-P has been suggested to modulate cell adhesion and tumor formation. Although we have previously shown that downregulation of Betaig-h3 gene is involved in the cellular transformation of human bronchial epithelial cells induced by radiation, its regulation in primary human lung cancers is not clearly understood. In this study, Betaig-h3 expression was studied in 130 primary human lung carcinomas by immunohistochemistry. Betaig-h3 protein was absent or reduced by more than two-fold in 45 of 130 primary lung carcinomas relative to normal lung tissues examined. Recovery of Betaig-h3 expression in H522 lung cancer cells lacking endogenous Betaig-h3 protein significantly suppressed their in vitro cellular growth and in vivo tumorigenicity. In addition, parental H522 cancer cells are resistant to the etoposide induced apoptosis compared with normal human bronchial epithelial cells. However, recovery of Betaig-h3 expression in H522 cancer cells results in significantly higher sensitivity to apoptotic induction than parental tumor cells. IGFBP3 is upregulated in Betaigh3-transfected H522 cells that may mediate the apoptotic sensitivity and antitumor function of Betaig-h3 gene. These observations demonstrate that downregulation of Betaig-h3 gene is a frequent event and related to the tumor progression in human lung cancer. (c) 2005 Wiley-Liss, Inc.