Altered expression of estrogen receptor coregulators during human breast tumorigenesis

The hypothesis that altered expression of specific coactivators/repressors of the estrogen receptor occurs during human breast tumorigenesis in vivo i s examined in this study. Using in situ hybridization and reverse transcrip tion-PCR assays, the expression of two coactivators (SRA and AIB1) and one repressor (REA) of the estrogen receptor was compared between matched breas t tumors and adjacent normal human breast tissue. The levels of SRA and AIB 1 mRNA were increased in tumors compared with normal tissues (n = 19; Wilco xon matched pairs test; P < 0.01), In contrast, the expression of REA mRNA was not different between tumors and normal tissues (n = 19; Wilcoxon: P = 0.110). Thr: ratios of AIB1:REA and SRA:REA were higher (Wilcoxon; P < 0.05 ) in tumors compared with normal tissues. Furthermore, SRA:AIB1 was higher (Wilcoxon; P = 0.0058) in tumors compared with normal tissues. Although our study is small, these data are consistent with the above hypothesis and su ggest that such alterations may have a role in the altered estrogen action occurring during breast tumorigenesis.