Environmental Health Perspectives 105, Supplement 1, February 1997

Roles of Retinoids and Their Nuclear Receptors in the Development and Prevention of Upper Aerodigestive Tract Cancers

Reuben Lotan

Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Abstract
Vitamin A analogs (retinoids) suppress oral and lung carcinogenesis in animal models and prevent the development of second primary tumors in head, neck, and lung cancer patients. These effects result from changes in the expression of genes that regulate cell growth and differentiation. Retinoic acid receptors (RARs; -, -ß, and -) and retinoid X receptors (RXRs; -, -ß, and, -) are retinoid-activated transcription factors, which mediate effects of retinoids on gene expression. Therefore, alterations in receptor expression or function could interfere with the retinoid signaling pathway and thereby enhance cancer development. We found that the expression of RARß was suppressed in more than 50% of oral and lung premalignant lesions in individuals without cancer and 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 and RXRß was somewhat decreased in lung cancers. These results show that RARß expression is lost at early stages of carcinogenesis in the aerodigestive tract and support the hypothesis that the loss of RARß expression may facilitate the development of some of these cancers. -- Environ Health Perspect 105(Suppl 4):985-988 (1997)

Key words: retinoids, chemoprevention, nuclear receptors, lung cancer, oral cancer

This paper is based on a presentation at the symposium on Mechanisms and Prevention of Environmentally Caused Cancers held 21-25 October 1995 in Santa Fe, New Mexico. Manuscript received at EHP 16 April 1996; accepted 7 October 1996.
Address correspondence to Dr. R. Lotan, Department of Tumor Biology-108, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Telephone: (713) 792-7480. Fax: (713) 794-0209. E-mail: rlotan@tumorbo1.mda.uth.tmc.edu
Abbreviations used: ATRA, ß-all-trans-retinoic acid; HN, head and neck; HNSCC, head and neck squamous cell carcinoma; MAb, monoclonal antibody; NSCLC, non-small cell lung cancer; RA, retinoic acid; RAR, retinoic acid receptor; RXR, retinoid X receptor; 9cRA, 9-cis-retinoic acid; 13cRA, 13-cis-retinoic acid.
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Last Update: June 30, 1997