title: Tumor suppressor function of Betaig-h3 gene in radiation carcinogenesis.
abstract: Interaction between cell and extracellular matrix (ECM) plays a crucial role in tumor invasiveness and metastasis. Using an immortalized human bronchial epithelial (BEP2D) cell model, we showed previously that expression of a list of genes including Betaig-h3 (induced by transforming growth factor-beta), DCC (deleted in colorectal cancer), p21(cipl), c-fos, Heat shock protein (HSP27) and cytokeratin 14 were differentially expressed in several independently generated, radiation-induced tumor cell lines (TL1-TL5) relative to parental BEP2D cells. Our previous data further demonstrated that loss of tumor suppressor gene(s) as a likely mechanism of radiation carcinogenesis. In the present study, we chose Betaig-h3 and DCC that were downregulated in tumorigenic cells for further study. Restored expression of Betaig-h3 gene, not DCC gene, by transfecting cDNA into tumor cells resulted in a significant reduction in tumor growth. While integrin receptor alpha 5 beta 1 was overexpressed in tumor cells, its expression was corrected to the level found in control BEP2D cells after Betaig-h3 transfection. These data suggest that Betaig-h3 gene is involved in tumor progression by regulating integrin alpha 5 beta 1 receptor. Furthermore, exogenous TGF- beta 1 induced expression of Betaig-h3 gene and inhibited the growth of both control and tumorigenic BEP2D cells. Therefore, downregulation of Betaig-h3 gene may results from the decreased expression of upstream mediators such as TGF-beta. The findings provide strong evidence that the Betaig-h3 gene has tumor suppressor function in radiation-induced tumorigenic human bronchial epithelial cells and suggest a potential target for interventional therapy.
authors.affiliation: Center for Radiological Research, College of Physicians & Surgeons of Columbia University, New York, NY 10032, USA. yz93@columbia.edu
authors.forename: Y L
authors.initials: YL
authors.lastname: Zhao
authors.forename: C Q
authors.initials: CQ
authors.lastname: Piao
authors.forename: T K
authors.initials: TK
authors.lastname: Hei
mesh_terms: D000512:Alpha Particles; D000818:Animals; D001980:Bronchi / Q000166:cytology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000528:radiation effects*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000528:radiation effects; D016163:Genes, DCC; D016147:Genes, Tumor Suppressor; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta; D014407:Tumor Cells, Cultured; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D039081:Integrin alpha5beta1; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein