| Ah receptor antagonism represses head and neck tumor cell aggressive phenotype. | |
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MedLine Citation:
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PMID: 22912337 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 IL6 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 head and neck squamous cell carcinoma (HNSCC) patients. Constitutive activation of the AHR in HNSCC cells was blocked by antagonist treatment, leading to a reduction in IL6 expression. Additionally, the AHR exhibits a high level of expression in HNSCC cells compared to normal keratinocytes. These findings led to the hypothesis that the basal AHR activity in HNSCC cells 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 HNSCC through a reduction in aggressive cell phenotype. |
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Authors:
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Brett C Dinatale; Kayla Smith; Kaarthik John; Gowdahalli Krishnegowda; Shantu G Amin; Gary H Perdew |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-21 |
Journal Detail:
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Title: Molecular cancer research : MCR Volume: - ISSN: 1557-3125 ISO Abbreviation: Mol. Cancer Res. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101150042 Medline TA: Mol Cancer Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Pennsylvania State University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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