Expression of estrogen receptor |[alpha]|, retinoic acid receptor |[alpha]| and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells

摘要

Human breast cancer cell lines expressing the estrogen receptor (ER), all-trans-retinoic acid (ATRA) receptor (RAR) and cellular retinoic acid binding protein II (CRABPII) genes are sensitive to ATRA-mediated growth inhibition. To study the relationship among ER, RAR and CRABPII expression, the protein levels of each member were compared in five breast cancer cell lines (T47D, MCF-7, ZR-75-1, Hs587T and MDA-MB-231 cells) and two immortalized nontumorigenic breast epithelial cell lines (MTSV1.7 and MCF-10A). ER, RAR and CRABPII proteins were detected in T47D, MCF-7 and ZR-75-1 cells but not in other tested cell lines. RAR and CRABPII proteins were either reduced or undetectable in T47D/C4:2W and MCF-7/ADR cells with lost expression of ER. Estradiol increased and anti-estrogens (tamoxifen and ICI 164,384) downregulated the expression of both RAR and CRABPII proteins in T47D and MCF-7 cells. RAR antagonist Ro-41-5253 inhibited CRABPII expression, but not RAR expression in estradiol-treated T47D and MCF-7 cells. Suppression of ER by small interfering RNA (siRNA) reduced RAR and CRABPII gene expression and siRNA suppression of RAR reduced CRABPII expression while having no effect on ER in T47D cells. Transient transfection of either RAR or ER expression vectors increased CRABPII expression in MDA-MB-231 cells but only RAR, not ER, activated hCRABPII promoter reporter. These results indicate that there is a gene activation pathway in which ER drives RAR transcription and RAR drives CRABPII transcription in ER-positive human breast cancer cells.