Suppression of Retinoic Acid Receptor–β in Premalignant Oral Lesions and Its Up-Regulation by Isotretinoin

作者：Reuben Lotan, Xiaochun Xu, Scott M. Lippman, Jae Yoon Ro, Jin S. Lee, J. Jack Lee, Waun Ki Hong · 发表于：New England Journal of Medicine · 年份：1995 · DOI：10.1056/nejm199505253322103 · 被引用次数：412 · 研究领域：Retinoids in leukemia and cellular processes、Acne and Rosacea Treatments and Effects、Oral Health Pathology and Treatment

BACKGROUND: Retinoids are effective in the treatment and prevention of certain human cancers. Most of their actions are thought to result from changes in gene expression mediated by nuclear retinoic acid receptors and retinoid X receptors. We conducted a study to determine whether the expression of these receptors was altered in premalignant oral lesions and, if so, whether their expression could be restored by treatment with isotretinoin. METHODS: We performed in situ hybridization of retinoic acid receptors and retinoid X receptors using antisense riboprobes in specimens of oral mucosa from 7 normal subjects and specimens of premalignant oral lesions from 52 patients before treatment with isotretinoin and from 39 of the 52 patients after three months of treatment. RESULTS: All the normal specimens expressed retinoic acid receptor-beta messenger RNA (mRNA). In contrast, retinoic acid receptor-beta mRNA was detected in only 21 of the 52 premalignant oral lesions (P = 0.003). Thirty-five of the 39 specimens available for evaluation after treatment expressed retinoic acid receptor-beta mRNA (P < 0.001). All normal and premalignant specimens expressed similar levels of mRNA for retinoic acid receptor-alpha and retinoic acid receptor-gamma and the three types of retinoic X receptors, alpha, beta, and gamma. The levels of retinoic acid receptor-beta mRNA increased in the specimens from 18 of the 22 patients who had responses to isotretinoin and in 8 of the 17 specimens from the pa...