RETINOIC ACID RECEPTOR-ALPHA, RECEPTOR-BETA AND RECEPTOR-GAMMA, AND CELLULAR RETINOL-BINDING PROTEIN-I EXPRESSION IN BREAST FIBROCYSTIC DISEASE AND CANCER

Retinoids seem to act as agents of chemoprevention and differentiation in breast diseases. Their action is mediated by nuclear receptors, re tinoic acid receptors (RAR alpha, RAR beta, RAR gamma) and retinoid X receptors (RXR alpha, RXR beta, RXR gamma) and modulated by cellular r etinol binding proteins (CRBP). There are few published data on CRBP e xpression. In this study, we evaluated the expression of RAR alpha, be ta and gamma and CRBP type I (CRBP-I) gene expression in fibrocystic d isease (FD) and in breast cancer (BC), studying 14 FD and 20 BC surgic al samples by reverse transcription (RT)-PCR. We also evaluated mRNA c oncentrations in cancer samples by a semiquantitative PCR method, co-a mplifying RAR alpha, RAR beta and CRBP-I genes with an unrelated gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as internal control . All benign and malignant breast tissues expressed RAR alpha, beta an d gamma, and CRBP-I mRNAs. A greater concentration of RAR beta mRNA wa s detected in cancer tissues with lower oestrogen and progesterone rec eptor concentrations, whereas RAR alpha was detected in variable conce ntrations that were not related to those of steroid receptors. The CRB P-I concentration was similar in all samples studied. We demonstrated that all three RARs and CRBP-I transcripts are expressed in FD, and th at RAR beta, RAR gamma and CRBP-I mRNAs also are present in BC tissues . This indicates that both malignant and benign breast tissues may be target for retinoids, justifying the use of natural and synthetic vita min A derivatives in the chemoprevention of breast disease.