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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Early Changes in Gene Expression Induced by Tobacco Smoke: Evidence for the Importance of Estrogen within Lung Tissue

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Autor(es):
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Meireles, Sibele I. [1] ; Esteves, Gustavo H. [2] ; Hirata, Jr., Roberto [3] ; Peri, Suraj [4] ; Devarajan, Karthik [4] ; Slifker, Michael [4] ; Mosier, Stacy L. [1] ; Peng, Jing [1] ; Vadhanam, Manicka V. [5] ; Hurst, Harrell E. [5] ; Neves, E. Jordao [3] ; Reis, Luiz F. [6] ; Gairola, C. Gary [7] ; Gupta, Ramesh C. [5] ; Clapper, Margie L. [1]
Número total de Autores: 15
Afiliação do(s) autor(es):
[1] Fox Chase Canc Ctr, Canc Prevent & Control Program, Philadelphia, PA 19111 - USA
[2] Univ Paraiba State, Ctr Sci & Technol, Campina Grande - Brazil
[3] Univ Sao Paulo, Dept Math & Stat, Sao Paulo - Brazil
[4] Fox Chase Canc Ctr, Dept Biostat & Bioinformat, Philadelphia, PA 19111 - USA
[5] Univ Louisville, James Graham Brown Canc Ctr, Dept Pharmacol & Toxicol, Louisville, KY 40292 - USA
[6] Hosp Sirio Libanes, Sao Paulo - Brazil
[7] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY - USA
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: Cancer Prevention Research; v. 3, n. 6, p. 707-717, JUN 2010.
Citações Web of Science: 36
Resumo

Lung cancer is the leading cause of cancer deaths in the United States, 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/d, 5 d/wk for 3, 8, and 20 weeks). Gene expression profiles of lung tissue from control and smoke-exposed animals were established using a 15K cDNA microarray. Cytochrome P450 1b1, a phase I enzyme involved in both the metabolism of xenobiotics and the 4-hydroxylation of 17 beta-estradiol (E(2)), was modulated to the greatest extent following smoke exposure. A panel of 10 genes were found to be differentially expressed in control and smoke-exposed lung tissues at 3, 8, and 20 weeks (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, E(2) 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 E2 within lung tissue when combined with the modulation of cytochrome P450 1b1 and other estrogen metabolism genes by tobacco smoke provides novel insight into a possible role for estrogens in lung cancer. Cancer Prev Res; 3(6); 707-17. (C) 2010 AACR. (AU)

Processo FAPESP: 99/11962-9 - Fenômenos críticos em processos evolutivos e sistemas em equilíbrio
Beneficiário:Pablo Augusto Ferrari
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
Beneficiário:Fernando Augusto Soares
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 99/07390-0 - Cooperation for Analysis of Gene Expression - CAGE
Beneficiário:Hugo Aguirre Armelin
Linha de fomento: Auxílio à Pesquisa - Temático