Abstract

Deregulation of the retinoblastoma (pRB) tumor suppressor pathway is frequently observed in human cancer and associated with aberrant activity of E2F transcription factors. We have performed microarray based analysis with the aim of identifying potential downstream mediators of the tumor suppressing activity of pRB. Here we report that the expression of LAP2 (lamina-associated polypeptide 2) is under direct control of E2F transcription factors. Chromatin immunoprecipitation assays show that the LAP2 promoter is bound by endogenous E2F in vivo. The LAP2 promoter is transactivated by ectopically expressed E2F and mutation of E2F binding sites eliminates this effect. We studied the expression level of LAP2 a in human tumors by tissue microarray analysis and found LAP2 a over expression in a significant percentage of primary larynx, lung, stomach, breast, and colon cancer tissues. In agreement with its regulation by E2F, LAP2 a over expression in primary tumors was found to be correlated with tumor proliferation rate.