Expression levels of estrogen receptor-alpha, estrogen receptor-beta, coactivators, and corepressors in breast cancer

Recent studies hare indicated that a complex machinery of transactivation o f target genes by estrogen or antiestrogen through estrogen receptor (ER) e xists. However, the substantial roles of ER-beta coactivators, and corepres sors in the development and progression of breast cancer remain to be eluci dated, To obtain some clue to these roles, we screened the expression level s of ER-alpha, ER-beta, coactivators (SRC-1, TIF2, AIB1, CBP, and P/CAF) an d corepressors (N-CoR and SMRT) in 6 normal mammary glands, 6 intraductal c arcinomas, 22 invasive ductal carcinomas, and 7 breast cancer cell lines us ing a multiples reverse transcription-PCR, ER-alpha mRNA expression levels significantly correlated dth ER-alpha protein levels measured by enzyme imm unoassay in the breast cancer tissues and cell. Lines. A significant correl ation of expression levels was observed between ER-alpha and TIF2, AIB1, P/ CAF, and N-CoR, and between ER-beta and AIB1 and CBP in the tissue samples. A. significant correlation was also observed between ER-alpha and ER-beta and between ER-beta and CBP in the cell Lines. The expression levels of ER- alpha TIF2, and CBP were significantly higher in the intraductal carcinomas than those in the normal mammary glands, In addition, the expression level s of ER-alpha. and N-CoR were significantly higher in the intraductal carci nomas than those in the invasive ductal carcinomas. These findings suggest a positive correlation of expression levels among ER-alpha and cofactors an d among ER-beta and cofactors, an up-regulation of expression levels of ER- alpha and cofactors during the development of intraductal carcinomas from n ormal mammary glands, and a decrease in their expression levels during the progression of breast cancer.