Retinoic acid receptor β2 gene in breast cancer

Abstract

BACKGROUND Retinoids, derivatives of vitamin A, with antiproliferative and proapoptotic capacities, are involved in crucial biological processes and could suppress carcinogenesis. Such characteristics might include them within the list of chemopreventive agents against breast cancer. Retinoic acid receptor-? (RAR?) has four isoforms with different biological functions. Defected expression of RAR?2 through cancer development could lead to tumorigenesis and retinoid resistance. Focusing on the gene interaction, the aberrant hypermethylation of RAR?2 and ER? genes was observed in a considerable proportion of a group of our breast cancer patients. Highlighting the importance of cancer family history as a preliminary risk factor, familial breast cancer was inversely associated with the hypermethylated RAR?2. Other environmental factors including obesity, duration of estradiol exposure, and smoking were believed as stimulator/predisposing factors for further development of methylation in ER? gene. The levels of plasma folate and vitamin B12 were inversely correlated with the hyperethylated ER? gene as well. CONCLUSION These data suggest the performance of multitarget investigation by including the molecular/cellular genetics, pedigree-based analysis, and bridging the results to clinic. This review ladders the known molecular and cell biological facts about RAR?2 in breast cancer. However, based on the available results, investigation of interactions between RAR? 2 and other genes might shed light to achieving the new prognostic-based strategies, innovation of biomarker, and therapeutic protocol for an appropriate clinical management of breast cancer patients.