| Rb dephosphorylation and suppression of E2F activity in human breast tumor cells exposed to a pharmacological concentration of estradiol. | |
| | |
MedLine Citation:
|
PMID: 11368161 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
This report characterizes the influence of a pharmacological concentration of estradiol on growth arrest and cell death in MCF-7 breast tumor cells, with a focus on elements of the Rb-E2F cell-cycle regulatory pathway. Continuous exposure of MCF-7 breast tumor cells to 100 microM estradiol produces a marked reduction in the G1 and S phase populations and a corresponding increase in the G2/M population within 24 h; after 48 h, accumulation of cells in G1 becomes evident while after 72 h the cells appear to be equally distributed between the G1 and G2/M phases. The accumulation of cells in G1 is temporally associated with dephosphorylation of the Rb protein and suppression of E2F activity. Estradiol also produces an initial burst of cell death with loss of approximately 40% of the tumor cell population within 24 h; however, there is no tangible evidence for the occurrence of apoptosis based on terminal transferase end-labeling of DNA, DNA fragmentation analysis by alkaline unwinding, cell-cycle analysis or cell morphology. In addition to the lack of caspase-3 in MCF-7 cells, the absence of apoptosis could be related, at least in part, to the fact that estradiol promotes a rapid reduction in levels of the E2F-1 and Myc proteins. Overall, these studies are consistent with the concept that alterations in the levels and/or activity of the E2F family of proteins as well as proteins interacting with the E2F family may influence the nature of the antiproliferative and cytotoxic responses of the breast tumor cell. |
| | |
Authors:
|
D A Gewirtz; Y M Di; J K Randolph; P T Jain; K Valerie; S Bullock; N Nath; S P Chellappan |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: Archives of biochemistry and biophysics Volume: 388 ISSN: 0003-9861 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 2001 Apr |
Date Detail:
|
Created Date: 2001-05-22 Completed Date: 2001-05-24 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: United States |
Other Details:
|
Languages: eng Pagination: 243-52 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology, Toxicology and Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA. gewirtz@hsc.vcu.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Apoptosis* Breast Neoplasms Carrier Proteins* Cell Cycle Proteins* Cell Division / drug effects Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Cyclins / metabolism DNA-Binding Proteins / metabolism E2F Transcription Factors E2F1 Transcription Factor E2F4 Transcription Factor Estradiol / pharmacology* Gene Expression / drug effects Humans Microtubule-Associated Proteins / metabolism Phosphorylation / drug effects Retinoblastoma Protein / metabolism* Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors / antagonists & inhibitors*, metabolism, physiology Tumor Cells, Cultured Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins* |
| Chemical | |
Reg. No./Substance:
|
0/CDKN1A protein, human; 0/Carrier Proteins; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/DNA-Binding Proteins; 0/E2F Transcription Factors; 0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/E2F4 Transcription Factor; 0/Microtubule-Associated Proteins; 0/Retinoblastoma Protein; 0/Retinoblastoma-Binding Protein 1; 0/Transcription Factor DP1; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 50-28-2/Estradiol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Stimulatory effect of basic fibroblast growth factor on induction of heat shock protein 27 in osteob...
Next Document: Mutational analyses of Aquifex pyrophilus DNA ligase define essential domains for self-adenylation a...