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Progressive Decrease in Nuclear Retinoic Acid Receptor ß Messenger RNA Level during Breast Carcinogenesis¹

Departments of Clinical Cancer Frevention [X-C. X., X. L., S. M. L.], tumor Biology [R. L.], Pathology [N. S., R. N.], Biomathematics [J. J. L.], Epidemiology [F. L.], and Breast Medical Oncology [G. H., K. D.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Some of the nuclear retinoic acid receptors (RARs) , ß, and and retinoid X receptors (RXRs) , ß, and are thought to mediate the effects of retinoids on cell growth, differentiation, and apoptosis and thereby prevent breast carcinogenesis. We analyzed the expression of mRNAs for the three RARs and RXR- in histological sections of specimens from 70 breast cancer patients, which included adjacent normal tissue, ductal carcinoma in situ, and invasive cancer, using in situ hybridization. RARs , ß, and and RXR- were expressed in 98.1, 98.0, 93.0, and 100% of the adjacent normal tissues. Significant decreases in the number of cases expressing RAR-ß were observed among ductal carcinoma in situ (83.1%) and invasive carcinomas (51.6%), especially among the poorly differentiated cases (77.4 and 35.7%, respectively). No relationship was found between the expression of estrogen receptor and RAR-ß. These results implicate decreases in RAR-ß expression in breast cancer development and suggest that they are independent of estrogen receptor status.

¹ Supported in part by grants from the Nelly Connally Breast Cancer Research Fund (to R. L.) and CN-45006-32 from the National Cancer Institute (to K. D.).

² Present address: Department of Medical Cancer Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.

³ To whom requests for reprints should be addressed, at the Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 236 Houston, TX 77030. Phone: (713) 792-7480; Fax: (713) 794-0209.

Received 9/ 3/97. Accepted 10/ 2/97.

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