Abstract
Previously we found that cigarette smoke depleted vitamin A in the lungs and induced tracheal precancerous lesions. To understand the molecular consequences underlying cigarette smoke-induced vitamin A depletion and its associated lung cancer risk, this study investigated the lung cancer-related genes in cigarette smoke-exposed rats with or without dietary retinoic acid, the active metabolite of vitamin A. Twenty-four male weanling rats were fed either a control or a retinoic acid supplemented diet. Half of each group was exposed to 40 commercial cigarettes/ d, 5 d/ wk. After 4 weeks, the rats were sacrificed and their lungs were immediately frozen. Total RNA was extracted and purified, from which cDNA was synthesized and labeled for gene expression analysis. Expressions of 120 genes were measured via a customized microarray. In lungs exposed to cigarette smoke, most of the genes involved in cell division, transcription and cell adhesion were up-regulated. The dietary retinoic acid treatment of the cigarette smoke-exposed lungs was found to down-regulate most of the genes involved in similar functions. In addition, retinoic acid down-regulated four genes, Egr1, Fos, Icam1 and Mmp9, all of which were up-regulated by cigarette smoke. These findings suggest possible molecular mechanisms of cigarette smoke induced-lung cancer and define potential targets of retinoic acid anticarcinogenic actions.
Highlights
Lung cancer is the leading cause of cancer-related death in both sexes worldwide [1], and in the United States [2]
In this study we investigated the regulation of genes related to cigarette smoke induced-lung cancer risk via customized microarrays and what role dietary retinoic acid played in such an event in a rodent model
It was observed that cigarette smoke exposure for 4 wk substantially increased the expression of transcription factor genes and genes involved in cell division and apoptosis in the lungs
Summary
Lung cancer is the leading cause of cancer-related death in both sexes worldwide [1], and in the United States [2]. Most cases of lung cancers are diagnosed after the disease has metastasized. Extensive studies have indicated that vitamin A may be a potential agent in lung cancer prevention at an early stage. Vitamin A deficiency has been shown to be associated with bronchial metaplasia and an increased incidence of lung cancer [3]. We have found that exposure to cigarette smoke deceases vitamin A levels in the lungs and results in precancerous lesions in the trachea [4]. The molecular mechanisms by which lung cancer is induced by cigarette smoke and how that is related to vitamin A deficiency is complicated. Numerous components have been suggested to be involved in the process
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