Characterization of a Putative Tumor Suppressor in Breast Cancer
Annual summary rept. 1 Jun 2001-31 May 2002
TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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The RASSF1A locus at 3p21.3 is epigenetically inactivated at high frequency in a variety of solid tumors. We have shown that expression of RASSF1A is sufficient to revert the tumorigenicity of human cancer cell lines. We have shown that RASSF1A can induce cell-cycle arrest by engaging the Rb-family cell cycle checkpoint. RASSF1A inhibits accumulation of native cyclin D1, and the RASSF1A-induced cell-cycle arrest can be relieved by ectopic expression of cyclin D1 or of other downstream activators of the G1-S phase transition cyclin A and E7. Regulation of cyclin D1 is responsive to native RASSF1A activity, as RNAi mediated down regulation of endogenous RASSF1A expression in human mammary epithelial cells results in abnormal accumulation of cyclin D1 protein.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research