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
Yongliang
Y
Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
El-Gabry
Mona
M
Hei
Tom K
TK
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015197:Carcinogenicity Tests; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein