Document Detail


Malignant Transformation of Mammary Epithelial Cells by Ectopic Overexpression of the Aryl Hydrocarbon Receptor.
MedLine Citation:
PMID:  21486221     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The aryl hydrocarbon receptor (AhR) is a ligand activated basic helix-loop-helix transcription factor that binds to environmental poly aromatic hydrocarbons (PAH) and mediates their toxic and carcinogenic responses. There is ample documentation for the role of AhR in PAH-induced carcinogenicity. However, in this report we addressed whether overexpression of AhR alone is sufficient to induce carcinogenic transformation in human mammary epithelial cells (HMEC). Retroviral expression vectors were used to develop a series of stable cell lines expressing varying levels of AhR protein in an immortalized normal HMEC with relatively low endogenous AhR expression. The resulted increase in AhR expression and activity correlated with the development of cellular malignant phenotypes, most significantly epithelial-to-mesenchymal transition. Clones overexpressing AhR by more than 3-fold, exhibited a 50% decrease in population doubling time. Cell cycle analysis revealed that this increase in proliferation rates was due to an enhanced cell cycle progression by increasing the percentage of cells transiting into S- and G2/M phases. Cells overexpressing AhR exhibited enhanced motility and migration. Importantly, these cells acquired the ability to invade matrigel matrix, where more than 80% of plated cells invaded the matrigel matrix within 24 h, whereas none of parental or the vector control HMEC were able to invade matrigel. Collectively, these data provide evidence for a direct role of AhR in the progression of breast carcinoma. The results suggest a novel therapeutic target that could be considered for treatment and prevention of breast cancer progression.
Authors:
Brooks J; Eltom S E
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-13
Journal Detail:
Title:  Current cancer drug targets     Volume:  -     ISSN:  1873-5576     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101094211     Medline TA:  Curr Cancer Drug Targets     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Graduate Program in Pharmacology, Meharry Medical College, Nashville, TN 37208, USA. jbrook5@emory.edu.
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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