IngentaConnect Retinoids and chemoprevention of aerodigestive tract cancers

Abstract:

Natural and synthetic vitamin A metabolites and analogs (retinoids) were found to suppress head and neck and lung carcinogenesis in animal models and inhibit carcinogenesis in individuals with premalignant lesions and a high risk to develop cancer of the aerodigestive tract. Likewise, retinoids prevent the development of second primary cancers in head and neck and lung cancer patients who had been treated for the first primary. These effects are thought to result from changes in the expression of genes that regulate cell growth and differentiation. Most of the effects of retinoids on gene expression are mediated by nuclear retinoic acid receptors RARs ( agr , bgr , and ggr ) and retinoid X receptors (RXR agr , bgr , and ggr ), which function as retinoid-activated transcription factors. Like vitamin A deficiency, alterations in receptor expression or function could interfere with the retinoid signaling pathway and thereby enhance cancer development even in vitamin A sufficient individuals. We found that the expression of RAR bgr was suppressed in more than 50% of oral and lung premalignant lesions in individuals without cancer (e.g., oral leukoplakia and squamous metaplasia), in dysplastic lesions adjacent to cancer, and in malignant oral and lung carcinomas. The expression of the other receptors was not different among normal, dysplastic, and malignant oral tissues. However, the expression of RAR ggr and RXR bgr was somewhat decreased in lung cancers. These results show that RAR bgr expression is lost at early stages of carcinogenesis in the aerodigestive tract and support the hypothesis that the loss of RAR bgr expression may facilitate the development of some of these cancers.

Keywords: retinoids; retinoic acid; cancer chemoprevention; aerodigestive; premalignant lesion

Language: English

Document Type: Regular paper

Affiliations: 1: Department of Tumor Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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