Tumor-suppressive activity of retinoic acid receptor-β in cancer

Retinoids, a group of structural and functional analogs of vitamin A, are known to regulate a large number of essential biological processes and to suppress carcinogenesis. The effects of retinoids are mainly mediated by nuclear retinoid receptors, which include retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Each receptor has three subtypes (α, β, and γ) and each subtype has different isoforms. Retinoic acid receptor-β (RAR-β) has four isoforms that have different affinities to retinoids and different biological functions. Loss of expression of RAR-β2 during cancer development is associated with tumorigenesis and retinoid resistance; induction of its expression, on the other hand, can suppress carcinogenesis. Expression of another isoform, RAR-β4, is increased in various types of cancer. RAR-β4 transgenic mice develop hyperplasia and neoplasia in various tissues, and induction of RAR-β4 expression increases the growth of tumor cells that do not express RAR-β2. Future studies will focus on molecular pathways involving RAR-β2 and the role of RAR-β4 in cancer development.