Loss of Betaig-h3 protein is frequent in primary lung carcinoma and related to tumorigenic phenotype in lung cancer cells.

Betaig-h3 as a secreted protein induced by transforming growth factor-beta 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.

Zhao Y ，El-Gabry M ，Hei TK 《MOLECULAR CARCINOGENESIS》

Downregulation of Betaig-h3 gene is causally linked to tumorigenic phenotype in asbestos treated immortalized human bronchial epithelial cells.

Zhao YL ，Piao CQ ，Hei TK 《ONCOGENE》

BetaIg-h3 is involved in the HAb18G/CD147-mediated metastasis process in human hepatoma cells.

Tang J ，Zhou HW ，Jiang JL ，Yang XM ，Li Y ，Zhang HX ，Chen ZN ，Guo WP ... -  《-》

Epigenetic inactivation of Betaig-h3 gene in human cancer cells.

Shao G ，Berenguer J ，Borczuk AC ，Powell CA ，Hei TK ，Zhao Y ... -  《CANCER RESEARCH》

The extracellular matrix protein betaIG-H3 is expressed at myotendinous junctions and supports muscle cell adhesion.

Ferguson JW ，Thoma BS ，Mikesh MF ，Kramer RH ，Bennett KL ，Purchio A ，Bellard BJ ，LeBaron RG ... -  《CELL AND TISSUE RESEARCH》