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Retinoids and chemoprevention of aerodigestive tract cancers
Author(s): Lotan R
Source: CANCER AND METASTASIS REVIEWS    Volume: 16    Issue: 3-4    Pages: 349-356    Published: SEP-DEC 1997  
Times Cited: 28     References: 40     
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 (alpha, beta, and gamma) and retinoid X receptors (RXR alpha, beta, and gamma), 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 beta 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 gamma and RXR beta was somewhat decreased in lung cancers. These results show that RAR beta expression is lost at early stages of carcinogenesis in the aerodigestive tract and support the hypothesis that the loss of RAR beta expression may facilitate the development of some of these cancers.
Document Type: Review
Language: English
Reprint Address: Lotan, R (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Tumor Biol 108, 1515 Holcombe Blvd, Houston, TX 77030 USA
Addresses:
1. Univ Texas, MD Anderson Cancer Ctr, Dept Tumor Biol 108, Houston, TX 77030 USA
Publisher: KLUWER ACADEMIC PUBL, SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
Subject Category: Oncology
IDS Number: YL635
ISSN: 0167-7659
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