Retinoid-resistant estrogen receptor-negative human breast carcinoma cells transfected with retinoic acid receptor-alpha acquire sensitivity to growth inhibition by retinoids.

摘要: Retinoids mediate their actions via RARs (retinoic acid receptors) and RXRs (retinoid X receptors). Each class of these nuclear retinoid receptors is further subdivided into three species, namely alpha, beta, gamma. Recent studies demonstrate that estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines tumor samples exhibit significantly higher levels RAR alpha than ER-negative counterparts. ER-positive HBC are sensitive to, resistant growth inhibitory effects retinoic (RA). We previously demonstrated the expression functional ERs in an established line resulted sensitivity to inhibition by RA. To investigate major role retinoid-mediated growth, we transfected cDNA two RA-resistant lines. Analyses different clonal populations transfectants from each revealed retinoids. Utilizing RAR- RXR-class selective retinoids, only alpha-selective retinoids mediated cells, while RXR-selective were biologically inert. thus provide evidence molecular mechanisms proliferation predominantly involve alpha.