Effects of cigarette smoke on the human oral mucosal transcriptome Journal Article
| Authors: | Boyle, J. O.; Gümüş, Z. H.; Kacker, A.; Choksi, V. L.; Bocker, J. M.; Zhou, X. K.; Yantiss, R. K.; Hughes, D. B.; Du, B.; Judson, B. L.; Subbaramaiah, K.; Dannenberg, A. J. |
| Article Title: | Effects of cigarette smoke on the human oral mucosal transcriptome |
| Abstract: | Use of tobacco is responsible for ∼30% of all cancer-related deaths in the United States, including cancers of the upper aerodigestive tract. In the current study, 40 current and 40 age- and gender-matched never smokers underwent buccal biopsies to evaluate the effects of smoking on the transcriptome. Microarray analyses were carried out using Affymetrix HGU133 Plus 2 arrays. Smoking altered the expression of numerous genes: 32 genes showed increased expression and 9 genes showed reduced expression in the oral mucosa of smokers versus never smokers. Increases were found in genes involved in xenobiotic metabolism, oxidant stress, eicosanoid synthesis, nicotine signaling, and cell adhesion. Increased numbers of Langerhans cells were found in the oral mucosa of smokers. Interestingly, smoking caused greater induction of aldo-keto reductases, enzymes linked to polycyclic aromatic hydrocarbon - induced genotoxicity, in the oral mucosa of women than men. Striking similarities in expression changes were found in oral compared with the bronchial mucosa. The observed changes in gene expression were compared with known chemical signatures using the Connectivity Map database and suggested that geldanamycin, a heat shock protein 90 inhibitor, might be an antimimetic of tobacco smoke. Consistent with this prediction, geldanamycin caused dose-dependent suppression of tobacco smoke extract - mediated induction of CYP1A1 and CYP1B1 in vitro. Collectively, these results provide new insights into the carcinogenic effects of tobacco smoke, support the potential use of oral epithelium as a surrogate tissue in future lung cancer chemoprevention trials, and illustrate the potential of computational biology to identify chemopreventive agents. ©2010 AACR. |
| Keywords: | signal transduction; adult; controlled study; human tissue; middle aged; unclassified drug; case-control studies; cigarette smoking; gene expression; gene expression profiling; tumor markers, biological; smoking; in vitro study; gene expression regulation; immunoenzyme techniques; blotting, western; reverse transcriptase polymerase chain reaction; rna, messenger; microarray analysis; oligonucleotide array sequence analysis; cigarette smoke; heat shock protein 90; nicotine; sex difference; oxidative stress; cytochrome p450 1b1; bronchus mucosa; oxidoreductase; cell adhesion; mouth mucosa; transcriptome; bronchi; normal human; fatty acid synthesis; genotoxicity; cytochrome p450 1a1; human experiment; geldanamycin; aldo keto reductase; icosanoid; polycyclic aromatic hydrocarbon; carcinogenic activity; langerhans cell; oral biopsy; xenobiotic metabolism; langerhans cells |
| Journal Title: | Cancer Prevention Research |
| Volume: | 3 |
| Issue: | 3 |
| ISSN: | 1940-6207 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-03-01 |
| Start Page: | 266 |
| End Page: | 278 |
| Language: | English |
| DOI: | 10.1158/1940-6207.capr-09-0192 |
| PUBMED: | 20179299 |
| PROVIDER: | scopus |
| PMCID: | PMC2833216 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 20 April 2011" - "Source: Scopus" |
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