Overexpression of Betaig-h3 gene downregulates integrin α5β1 and suppresses tumorigenicity in radiation-induced tumorigenic human bronchial epithelial cells

Abstract

Interaction between cell and extracellular matrix plays a crucial role in tumour invasion and metastasis. Using an immortalised human bronchial epithelial (BEP2D) cell model, the study here shows that expression of Betaig-h3 gene, which encodes a secreted adhesion molecule induced by transforming growth factor-β, is markedly decreased in several independently generated, radiation-induced tumour cell lines (TL1 - TL5) relative to parental BEP2D cells. Transfection of Betaig-h3 gene into tumour cells resulted in a significant reduction in tumour growth. While integrin receptor α5β1 was overexpressed in tumour 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 tumour progression by regulating integrin receptor α5β1. The findings provide strong evidence that the Betaig-h3 gene has tumour suppressor function in human BEP2D cell model and suggest a potential target for interventional therapy. © 2002 Cancer Research UK.