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MOLECULAR PHARMACOLOGY 52:373-379 (1997).

Ionizing Radiation and Teniposide Increase p21^waf1/cip1 and Promote Rb Dephosphorylation but Fail to Suppress E2F Activity in MCF-7 Breast Tumor Cells

Michael S. Orr,¹ Nicole C. Watson, Sujatha Sundaram, Joyce K. Randolph, Pramod T. Jain, and David A. Gewirtz

Department of Pharmacology/Toxicology and Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298

Ionizing radiation and the topoisomerase II inhibitor, teniposide (VM-26) both increase levels of the cyclin dependent kinase inhibitor, p21^waf1/cip1 and promote dephosphorylation of the retinoblastoma tumor suppressor protein, Rb, in MCF-7 breast tumor cells, perturbations associated with suppression of the activity of the transcription factor, E2F. However, studies using an E2F binding site-luciferase reporter plasmid transfected into MCF-7 cells failed to demonstrate a reduction in E2F activity in response to VM-26 or to ionizing radiation. In contrast, E2F activity (both basal and E1A stimulated) could be suppressed by transfection with a plasmid expressing Rb, indicating that the capacity of E2F to bind to Rb and to be inactivated by Rb is functionally intact in MCF-7 cells. These findings in MCF-7 breast tumor cells suggest that E2F activity may not be directly susceptible to modulation by endogenous p21^waf1/cip1 and Rb.