title: Ionizing radiation and teniposide increase p21(waf1/cip1) and promote Rb dephosphorylation but fail to suppress E2F activity in MCF-7 breast tumor cells.
abstract: 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.
authors.affiliation: Department of Pharmacology/Toxicology and Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Orr
authors.forename: N C
authors.initials: NC
authors.lastname: Watson
authors.forename: S
authors.initials: S
authors.lastname: Sundaram
authors.forename: J K
authors.initials: JK
authors.lastname: Randolph
authors.forename: P T
authors.initials: PT
authors.lastname: Jain
authors.forename: D A
authors.initials: DA
authors.lastname: Gewirtz
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids; D016160:Retinoblastoma Protein / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D056465:Retinoblastoma-Binding Protein 1; D015398:Signal Transduction / Q000502:physiology; D013713:Teniposide / Q000494:pharmacology*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D013713:Teniposide; D008156:Luciferases