Restoring Retinoid Signals in Cancer Cells

Abstract

STKE Retinoids have multiple biological effects, including inhibition of proliferation of certain cancer cells. The retinoids often act through heterodimers of two nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). In normal cells, the expression of RARb is enhanced through transcriptional activation in response to retinoids, but many cancer cell lines lose their ability to response even though the RAR and RXR proteins are still expressed. Lin et al. now show that such retinoid-insensitive cells may be missing another nuclear receptor, the orphan receptor COUP-TF. In cancer cell lines lacking COUP-TF, expression of COUP-TF restored retinoid-induced expression of RARb as well as the apoptotic and growth inhibitory effects of retinoic acid in these cells. COUP-TF appears to enhance the interaction of RAR with the transcriptional coactivator CBP through DNA binding. This mechanism of action of COUP-TF is distinct from its effects on other genes, where it has its own transactivation activity through recruitment of a different coactivator.— LBR Mol. Cell. Biol. 20 , 957 (2000).