Early changes in gene expression induced by tobacco smoke: Evidence for the importance of estrogen within lung tissue.
Early changes in gene expression induced by tobacco smoke: Evidence for the importance of estrogen within lung tissue.
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DOI：
10.1158/1940-6207.capr-09-0162
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Clapper ML
中科院分区：
文献类型：
--
作者：
Meireles SI;Esteves GH;Hirata R Jr;Peri S;Devarajan K;Slifker M;Mosier SL;Peng J;Vadhanam MV;Hurst HE;Neves EJ;Reis LF;Gairola CG;Gupta RC;Clapper ML
Lung cancer is the leading cause of cancer deaths in the U.S., surpassing breast cancer as the primary cause of cancer-related mortality in women. The goal of the present study was to identify early molecular changes in the lung induced by exposure to tobacco smoke and thus identify potential targets for chemoprevention. Female A/J mice were exposed to either tobacco smoke or HEPA-filtered air via a whole-body exposure chamber (6 h/day; 5 days/wk for 3, 8 and 20 wk). Gene expression profiles of lung tissue from control and smoke-exposed animals were established using a 15 K cDNA microarray. Cytochrome P450 1b1 (Cyp1b1), a Phase I enzyme involved in both the metabolism of xenobiotics and the 4-hydroxylation of 17β-estradiol, was modulated to the greatest extent following smoke exposure. A panel of 10 genes was found to be differentially expressed in control and smoke-exposed lung tissue at 3, 8 and 20 wk (P < 0.001). The interaction network of these differentially expressed genes revealed new pathways modulated by short-term smoke exposure including estrogen metabolism. In addition, 17β-estradiol was detected within murine lung tissue by gas chromatography coupled mass spectrometry and immunohistochemistry. Identification of the early molecular events that contribute to lung tumor formation is anticipated to lead to the development of promising targeted chemopreventive therapies. In conclusion, the presence of 17β-estradiol within lung tissue when combined with the modulation of Cyp1b1 and other estrogen metabolism genes by tobacco smoke provides novel insight into a possible role for estrogens in lung cancer.
