Retinoic acid receptors alpha, beta and gamma, and cellular retinol binding protein-I expression in breast fibrocystic disease and cancer.

Abstract

Retinoids seem to act as agents of chemoprevention and differentiation in breast diseases. Their action is mediated by nuclear receptors, retinoic acid receptors (RAR alpha, RAR beta, RAR gamma) and retinoid X receptors (RXR alpha, RXR beta, RXR gamma) and modulated by cellular retinol binding proteins (CRBP). There are few published data on CRBP expression. In this study, we evaluated the expression of RAR alpha, beta and gamma and CRBP type I (CRBP-I) gene expression in fibrocystic disease (FD) and in breast cancer (BC), studying 14 FD and 20 BC surgical samples by reverse transcription (RT)-PCR. We also evaluated mRNA concentrations in cancer samples by a semiquantitative PCR method, co-amplifying RAR alpha, RAR beta and CRBP-I genes with an unrelated gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as internal control. All benign and malignant breat tissues expressed RAR alpha, beta and gamma, and CRBP-I mRNAs. A greater concentration of RAR beta mRNA was detected in cancer tissues with lower oestrogen and progesterone receptor concentrations, whereas RAR alpha was detected in variable concentrations that were not related to those of steroid receptors. The CRBP-I concentration was similar in all samples studied. We demonstrated that all three RARs and CRBP-I transcripts are expressed in FD, and that 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 vitamin A derivatives in the chemoprevention of breast disease.