Hormonal Control of Folate Receptor Genes

Abstract

The two major human folate receptor (FR) isoforms, alpha and beta, are glycosyl phosphatidylinositol-anchored glycoproteins with limited expression in normal tissues including epithelial cells (FR alpha) and hematopoietic cells (FR beta). FR alpha plays a critical role during pregnancy in ensuring an adequate supply of folate to the fetus. FRs are a potential means of delivering a range of therapeutics in cancer and inflammatory diseases in a tissue-targeted manner. The FR alpha gene is under the exquisite control of steroid hormones which regulate the protein expression by diverse and nonclassical molecular mechanisms. The FR beta gene on the other hand is regulated by retinoid compounds through a nonclassical mechanism. The physiological mechanisms of FR gene regulation could be utilized to selectively enhance the receptor expression and consequently drug delivery to the target tissues. The soluble form of FR alpha may also be effectively utilized in this manner as a serum marker in the early detection of certain cancers. The in vitro and animal model studies in this field have advanced to a stage that warrants direct clinical trials to validate the proposed treatment modalities.