Document Detail


Induction of breast cancer in wild type p53 cells by BRCA1-IRIS overexpression.
MedLine Citation:
PMID:  20845286     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cells ability to evade cell death and to proliferate post geno-/cell-toxic stresses, likely leads to formation of cancer. Activation of p38MAPK and p53 following these stresses help protect cells against cancer development by initiating apoptosis. The duration of p38MAPK and p53 activation is regulated by the WIP1 phosphatase. BRCA1-IRIS triggers WIP1 expression in p53-dependent and -independent manner. BRCA1-IRIS triggers the expression and cytoplasmic localization of the mRNA stabilization and translation inducer, HuR that binds p53 and PPM1D mRNA. Hence, BRCA1-IRIS overexpression inactivates p38MAPK and/or p53 by upregulating WIP1 expression. BRCA1-IRIS abrogation of the homeostatic balance maintained by p38MAPK-p53-WIP1 pathway suppressed cell death induced by a lethal dose of UVC, high dosages of etoposide or H2O2, and allowed cells to survive and proliferate post geno-/cell-toxic stresses. This mechanism represents a new link between geno-/cell-toxic stress and aggressive breast cancer formation in p53 wild-type cells.
Authors:
Wael M Elshamy
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hawaii medical journal     Volume:  69     ISSN:  0017-8594     ISO Abbreviation:  Hawaii Med J     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2010-10-21     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  2984209R     Medline TA:  Hawaii Med J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  200-1     Citation Subset:  IM    
Copyright Information:
Hawaii Medical Journal Copyright 2010.
Affiliation:
Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA.
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MeSH Terms
Descriptor/Qualifier:
BRCA1 Protein / metabolism*
Breast Neoplasms / physiopathology*
Cell Line, Tumor
Cell Proliferation*
Female
Free Radicals / adverse effects
Genes, p53*
Humans
Phosphoprotein Phosphatases / metabolism
Ultraviolet Rays / adverse effects
Up-Regulation
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/BRCA1 Protein; 0/BRCA1 protein, human; 0/Free Radicals; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.1.3.16/protein phosphatase 2C
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