All-trans retinoic acid is capable of inducing folate receptor β expression in KG-1 cells

The high expression of folate receptor (FR) on cancer cells might be a potential target for cancer therapy. In this study, the FR-beta expression and the modulation effect of all-trans retinoic acid (ATRA) in a number of cancer cell lines were analyzed. The gateway of ATRA activity on FR-beta expression was further studied by a panel of retinoid activators and inhibitors. The results revealed that ATRA was capable of upregulating the expression of FR-beta protein in KG-1 cells in a dosage-dependent manner, not in KG-1a, NB4, HL60, 293, L1210, JAR, and Hela cells. FR-beta mRNA expression in KG-1 cells was higher when ATRA was present in culture medium at 10(-6) mol/L for 5 days, and it went down to baseline when ATRA was removed from the medium, vice versa. The upregulation of FR-beta expression in KG-1 cells by ATRA was not associated with cell proliferation and differentiation. In addition, activators of retinoid acid receptor (RAR)alpha and RAR gamma, CD336, and CD2781 also induced FR-beta expression. The induction of FR-beta expression by CD336 could be inhibited by RAR gamma antagonist CD2665; RAR beta agonist CD-417 and CD-2314 as well as retinoid X receptor (RXR) agonist LG100364 could not induce FR-beta expression. These results indicate that ATRA within a certain range of concentration could reversibly induce the expression of FR-beta in a dosage- and cell type-dependent manner, and its action in KG-1 cells might be associated with the signal transduction of retinoid receptor RAR alpha and RAR gamma, rather than RAR beta and RXRs.