| Smoking attenuates Transforming Growth Factor-β-mediated tumor suppression function through down-regulation of Smad3 in lung cancer. | |
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MedLine Citation:
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PMID: 22232600 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Epidemiological studies have demonstrated that most cases of lung cancers (85-90%) are directly attributable to cigarette smoking. Although much information has been gained about the effects of cigarette smoking on various signaling pathways causing lung cancer, nothing is known about the effect cigarette smoking on the TGF-β-induced tumor suppressor function in lung cancer. To address this issue, lung adenocarcinoma A549 and immortalized bronchial epithelial HPL1A cells were chronically treated with cigarette smoke condensate (CSC) and Dimethyl sulphoxide (DMSO, as a control) to mimic the conditions of long-term cigarette smoking. Prolonged exposure of these cells to CSC resulted in a decrease in Smad3 and Smad4 complex formation and TGF-β-mediated transcription due to reduced expression of Smad3. Long-term CSC treatment reduced apoptosis, increased cell viability, decreased TGF-β-mediated growth inhibition, and enhanced tumorigenicity. The decrease in apoptosis is due to the up-regulation of Bcl-2, which is a downstream target of Smad3. Re-expression of Smad3 in the CSC treated cells restored TGF-β signaling, increased apoptosis and decreased cell viability and tumorigenicity. Withdrawal of CSC treatment resulted in the restoration of Smad3 expression, reduction in cell viability and increased TGF-β-mediated growth inhibition. Expression of Smad3 is lower in lung tumors of current smokers compared to that observed in never-smokers. Collectively, these data provide evidence that cigarette smoking promotes tumorigenicity partly by abrogating TGF-β-mediated growth inhibition and apoptosis by reducing expression of Smad3. |
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Authors:
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Debangshu Samanta; Adriana L Gonzalez; Nagaraj S Nagathihalli; Fei Ye; David P Carbone; Pran K Datta |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-9 |
Journal Detail:
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Title: Cancer prevention research (Philadelphia, Pa.) Volume: - ISSN: 1940-6215 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101479409 Medline TA: Cancer Prev Res (Phila) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Cancer Biology, Vanderbilt University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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