Downregulation of Betaig-h3 gene is causally linked to tumorigenic phenotype in asbestos treated immortalized human bronchial epithelial cells
Downregulation of Betaig-h3 gene is causally linked to tumorigenic phenotype in asbestos treated immortalized human bronchial epithelial cells
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DOI：
10.1038/sj.onc.1205891
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发表时间：
2002-10-24
期刊：
影响因子：
8
通讯作者：
Hei, TK
中科院分区：
文献类型：
--
作者：
Zhao, YL;Piao, CQ;Hei, TK
尽管 Betaig-h3 基因被认为可以调节细胞粘附和肿瘤形成，但其生理功能尚不清楚。使用人乳头瘤病毒永生化人支气管上皮（BEP2D）细胞，我们发现石棉诱导的致瘤细胞中 Betaig-h3 表达显着降低。致瘤和对照 BEP2D 细胞的融合导致 Betaig-h3 基因表达恢复至对照水平并丧失致瘤表型。此外，石棉诱导的致瘤细胞中 Betaig-h3 基因的异位表达抑制了细胞的体外生长、贴壁独立表型以及裸鼠的致瘤性。 Betaig-h3基因在各种正常人体组织中普遍表达，但大脑除外，在大脑中表达很少或不表达。相比之下，与正常人类细胞或组织相比，在检查的 14 种不同组织学类型的人类肿瘤细胞系中，Betaig-h3 基因的表达降低或缺失。结果强烈表明，Betaig-h3 表达缺失是人类癌症中的常见事件，并且与石棉处理的 BEP2D 细胞中致瘤表型的获得有因果关系。
Although Betaig-h3 gene has been suggested to modulate cell adhesion and tumor formation, its physiological functions are not well understood. Using human papillomavirus immortalized human bronchial epithelial (BEP2D) cells, we found that Betaig-h3 expression was markedly decreased in asbestos-induced tumorigenic cells. Fusion of tumorigenic and control BEP2D cells resulted in the recovery of Betaig-h3 gene expression to control level and the loss of tumorigenic phenotype. Furthermore, ectopic expression of Betaig-h3 gene in asbestos-induced tumorigenic cells inhibited cell growth in vitro, anchorage independent phenotype, as well as tumorigenicity in nude mice. Betaig-h3 gene is ubiquitously expressed in various normal human tissues, with the exception of the brain, where there is little or no expression. In contrast, there was a decrease or absence in expression of the Betaig-h3 gene in 14 human tumor cell lines of diverse histological types examined, when compared with normal human cells or tissues. The result strongly suggests that loss of Betaig-h3 expression is a frequent event in human cancer and causally related to acquisition of tumorigenic phenotype in asbestos-treated BEP2D cells.