Document Detail


Ah receptor antagonism represses head and neck tumor cell aggressive phenotype.
MedLine Citation:
PMID:  22912337     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aryl hydrocarbon receptor (AhR) has been shown to play a role in an increasing number of cellular processes. Recent reports have linked the AhR to cell proliferation, cytoskeletal arrangement, and tumor invasiveness in various tumor cell types. The AhR plays a role in the de-repression of the interleukin (IL)6 promoter in certain tumor cell lines, allowing for increased transcriptional activation by cytokines. Here, we show that there is a significant level of constitutive activation of the AhR in cells isolated from patients with head and neck squamous cell carcinoma (HNSCC). Constitutive activation of the AhR in HNSCCs was blocked by antagonist treatment, leading to a reduction in IL6 expression. In addition, the AhR exhibits a high level of expression in HNSCCs than in normal keratinocytes. These findings led to the hypothesis that the basal AhR activity in HNSCCs plays a role in the aggressive phenotype of these tumors and that antagonist treatment could mitigate this phenotype. This study provides evidence that antagonism of the AhR in HNSCC tumor cells, in the absence of exogenous receptor ligands, has a significant effect on tumor cell phenotype. Treatment of these cell lines with the AhR antagonists 6, 2', 4'-trimethoxyflavone, or the more potent GNF351, decreased migration and invasion of HNSCC cells and prevented benzo[a]pyrene-mediated induction of the chemotherapy efflux protein ABCG2. Thus, an AhR antagonist treatment has been shown to have therapeutic potential in HNSCCs through a reduction in aggressive cell phenotype.
Authors:
Brett C DiNatale; Kayla Smith; Kaarthik John; Gowdahalli Krishnegowda; Shantu G Amin; Gary H Perdew
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-21
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  10     ISSN:  1557-3125     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-18     Completed Date:  2013-04-24     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1369-79     Citation Subset:  IM    
Affiliation:
Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / metabolism
Carcinoma, Squamous Cell / genetics,  metabolism*,  pathology*
Cell Line, Tumor
Cell Movement / drug effects
Cell Nucleus / drug effects,  metabolism
Cell Proliferation / drug effects
Cell Survival / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Head and Neck Neoplasms / genetics,  metabolism*,  pathology*
Humans
Indoles
Interleukin-6 / genetics,  metabolism
Neoplasm Invasiveness
Neoplasm Proteins / metabolism
Phenotype
Purines
Receptors, Aryl Hydrocarbon / antagonists & inhibitors*,  genetics,  metabolism
Transcription, Genetic / drug effects
Up-Regulation / drug effects
Grant Support
ID/Acronym/Agency:
ES004869/ES/NIEHS NIH HHS; ES019964/ES/NIEHS NIH HHS; R01 ES004869/ES/NIEHS NIH HHS; R01 ES019964/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/ABCG2 protein, human; 0/IL6 protein, human; 0/Indoles; 0/Interleukin-6; 0/N-(2-(3H-indol-3-yl)ethyl)-9-isopropyl-2-(5-methyl-3-pyridyl)purin-6-amine; 0/Neoplasm Proteins; 0/Purines; 0/Receptors, Aryl Hydrocarbon
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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