RT Journal Article
SR Electronic
T1 Ionizing Radiation and Teniposide Increase p21<sup>waf1/cip1</sup> and Promote Rb Dephosphorylation but Fail to Suppress E2F Activity in MCF-7 Breast Tumor Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 373
OP 379
DO 10.1124/mol.52.3.373
VO 52
IS 3
A1 Orr, Michael S.
A1 Watson, Nicole C.
A1 Sundaram, Sujatha
A1 Randolph, Joyce K.
A1 Jain, Pramod T.
A1 Gewirtz, David A.
YR 1997
UL http://molpharm.aspetjournals.org/content/52/3/373.abstract
AB Ionizing radiation and the topoisomerase II inhibitor, teniposide (VM-26) both increase levels of the cyclin dependent kinase inhibitor, p21waf1/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 p21waf1/cip1 and Rb.