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Microarray analysis of lung cancer‐related signaling pathways in cigarette smoke‐exposed rats with or without vitamin A supplementation
Author(s) -
Xue Yuan,
Wang Weiqun George,
Baybutt Richard
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1013
Subject(s) - retinoic acid , lung cancer , apoptosis , vitamin , smoke , lung , cancer , medicine , cancer research , endocrinology , biology , chemistry , biochemistry , gene , organic chemistry
Previously we have found that cigarette smoke depleted vitamin A in the lungs and induced tracheal precancerous lesions. To understand the molecular consequences underlying smoke‐induced vitamin A depletion and its associated cancer risk, this study investigated the lung cancer‐related signaling pathways in cigarette smoke‐exposed rats with or without vitamin A supplementation. Twenty‐four male weanling rats were fed either a control or retinoic acid (0.1g/kg of diet) supplemented diet. Half of the each group was exposed to 40 commercial cigarettes/d, 5 d/wk. After 4 weeks, the rats were sacrificed and the lungs were immediately frozen. Total RNA was extracted and purified, from which cRNA was synthesized and labeled for gene expression analysis. Expression of eighty genes related to lung cancer signaling was measured via a customized microarray. In cigarette smoke treated lungs, retinoic acid was found to prevent smoke‐induced increase of the Bax to Bcl2 ratio, which suggests enhanced apoptosis. Marker genes involved in p53 and NFkB pathways such as p53, Igfbp, Nfkb1 and Nfkbia were also underexpressed in smoke exposed lungs when supplemented with retinoic acid. In addition, retinoic acid decreased the expression of proliferation indicators: PCNA and jun. These data suggest that retinoic acid supplementation may reduce lung cancer risk caused by cigarette smoke at least through inducing apoptosis and interfering with the p53 and NFkB pathways. (Supported by Terry Johnson Center for Basic Cancer Research and Kansas Agriculture Experiment Station and College of Human Ecology SRO grant)