Increased integrin α 5 β 1 heterodimer formation and reduced c‐Jun expression are involved in integrin β 1 overexpression‐mediated cell growth arrest

Integrins, heterodimers of α and β subunits, are a family of cell surface molecules mediating cell–cell and cell–extracellular matrix interaction. The largest subgroup is formed by the β 1 subunit containing integrins which consist of 12 members with different ligand‐binding properties. We previously reported that overexpressed integrin β 1 subunit in the hepatocellular carcinoma cell line SMMC‐7721 imposed a growth inhibitory effect through the upregulation of p21 cip1 and p27 kip1 . In this study, we confirmed the growth inhibitory effect of β 1 subunit overexpression in different cancer cell lines. The upregulated CDK inhibitors induced by β 1 integrin overexpression were essential for this integrin‐mediated growth arrest. Reduced c‐Jun level after integrin β 1 overexpression plays an important role in the transcriptional activation of p21 through the Sp1 sites. Solely overexpressed β 1 subunit could induce the expression of diverse α subunit in different cell lines, among which α 5 subunit was found to be correlated with integrin β 1 ‐mediated growth arrest. Relative lack of ECM–integrin interaction might be a reason for integrin β 1 overexpression‐mediated growth arrest. These results helped us understand more about the mechanisms that integrins regulate cell growth. J. Cell. Biochem. 109: 383–395, 2010. © 2009 Wiley‐Liss, Inc.