Regulation of Human Aldehyde Oxidase Expression by Retinoic Acid Receptor in MCF-7 Human Breast Adenocarcinoma Cells

Abstract

Aldehyde oxidase (AOX) metabolizes various compounds, but its regulation is not well understood. Retinoic acid (RA) has two main isomers: all-trans RA (ATRA), which binds to retinoic acid receptor (RAR), and 9-cis-RA, which binds to RAR and retinoid X receptor (RXR). Although 9-cis-RA and RXR-selective agonists induce AOX1 in MCF-7 human breast adenocarcinoma cells, the role of RAR remains unclear. MCF-7 cells treated with RAR-selective agonists for 96 h showed increased AOX1 expression, which was concentration-dependent for the clinically relevant drugs ATRA and adapalene, as analyzed by real-time PCR. The pan-RAR antagonist AGN193109 or pretreatment with actinomycin D (RNA synthesis inhibitor) attenuated this induction. Targeted RARα knockdown by siRNA revealed partial regulation by this subtype. ELISA assay showed a disconnect between AOX1 mRNA and protein levels. These findings indicate that in MCF-7 cells, RAR regulates AOX1 mRNA but its role in controlling protein expression appears to involve additional regulatory mechanisms.