Early changes in pulmonary gene expression following tobacco exposure shed light on the role of estrogen metabolism in lung carcinogenesis.
This perspective on Meireles et al. (beginning on p. 707 in this issue of the journal) discusses the increasing evidence for the role of female steroid hormones in lung cancer development and progression. The novel work of Meireles et al. is the first evidence for the rapid upregulation by tobacco smoke of a key cytochrome P450 gene that can metabolize estrogens such as beta-estradiol to potentially carcinogenic catechol and quinine forms, as well as the first evidence for the colocalization of beta-estradiol and estrogen receptors in murine airway epithelium. Actions of estrogens that contribute to lung carcinogenesis, especially in the presence of tobacco smoke, may involve both reactive intermediates that damage DNA and steroid hormone receptor signaling that promotes growth.
University of Pittsburgh Cancer Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pennsylvania, USA. siegfriedjm@upmc.edu
Jill M
JM
Siegfried
D000429:Alcohol Oxidoreductases / Q000502:physiology; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D056931:Cryptochromes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000096:biosynthesis; D004967:Estrogens / Q000378:metabolism*; D002393:Estrogens, Catechol / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000209:etiology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
C538963:CRY1 protein, human; C538964:Cry1 protein, mouse; D056931:Cryptochromes; D004967:Estrogens; D002393:Estrogens, Catechol; D012333:RNA, Messenger; D014028:Tobacco Smoke Pollution; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; C014036:4-hydroxyestradiol; D000429:Alcohol Oxidoreductases; C531130:CBR3 protein, human; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1; D008550:Melatonin