Document Detail


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
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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


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