Expression Levels of Estrogen Receptor-α, Estrogen Receptor-β, Coactivators, and Corepressors in Breast Cancer

• Published in: Clinical cancer research 2000-02, Vol.6 (2), p.512-518
• Main Authors: KUREBAYASHI, J, OTSUKI, T, KUNISUE, H, TANAKA, K, YAMAMOTO, S, SONOO, H
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Breast - metabolism; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - surgery; DNA Primers; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Receptors, Estrogen - genetics; Repressor Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Trans-Activators - genetics; Transcription Factors - genetics; Transcription, Genetic; Tumor Cells, Cultured; Tumors
• ISSN: 1078-0432; 1557-3265

Recent studies have indicated that a complex machinery of transactivation of target genes by estrogen or antiestrogen through estrogen receptor (ER) exists. However, the substantial roles of ER-β, coactivators, and corepressors in the development and progression of breast cancer remain to be elucidated. To obtain some clue to these roles, we screened the expression levels of ER-α, ER-β, coactivators (SRC-1, TIF2, AIB1, CBP, and P/CAF) and corepressors (N-CoR and SMRT) in 6 normal mammary glands, 6 intraductal carcinomas, 22 invasive ductal carcinomas, and 7 breast cancer cell lines using a multiplex reverse transcription-PCR. ER-α mRNA expression levels significantly correlated with ER-α protein levels measured by enzyme immunoassay in the breast cancer tissues and cell lines. A significant correlation of expression levels was observed between ER-α and TIF2, AIB1, P/CAF, and N-CoR, and between ER-β and AIB1 and CBP in the tissue samples. A significant correlation was also observed between ER-α and ER-β and between ER-β and CBP in the cell lines. The expression levels of ER-α, TIF2, and CBP were significantly higher in the intraductal carcinomas than those in the normal mammary glands. In addition, the expression levels of ER-α and N-CoR were significantly higher in the intraductal carcinomas than those in the invasive ductal carcinomas. These findings suggest a positive correlation of expression levels among ER-α and cofactors and among ER-β and cofactors, an up-regulation of expression levels of ER-α and cofactors during the development of intraductal carcinomas from normal mammary glands, and a decrease in their expression levels during the progression of breast cancer.