Kurebayashi J, Otsuki T, Kunisue H, Tanaka K, Yamamoto S, Sonoo H
Department of Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, Japan.
Clin Cancer Res. 2000 Feb;6(2):512-8.
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-beta, 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-alpha, ER-beta, 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-alpha mRNA expression levels significantly correlated with ER-alpha protein levels measured by enzyme immunoassay in the breast cancer tissues and cell lines. A significant correlation 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 levels of ER-alpha 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-alpha and cofactors and among ER-beta and cofactors, an up-regulation of expression levels of ER-alpha 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.
近期研究表明，雌激素或抗雌激素通过雌激素受体（ER）对靶基因进行反式激活存在一个复杂机制。然而，ER-β、共激活因子和共抑制因子在乳腺癌发生发展中的重要作用仍有待阐明。为了探寻这些作用的线索，我们采用多重逆转录 - PCR 技术，检测了 6 例正常乳腺组织、6 例导管内癌、22 例浸润性导管癌以及 7 种乳腺癌细胞系中 ER-α、ER-β、共激活因子（SRC-1、TIF2、AIB1、CBP 和 P/CAF）和共抑制因子（N-CoR 和 SMRT）的表达水平。在乳腺癌组织和细胞系中，ER-α mRNA 表达水平与通过酶免疫测定法测得的 ER-α 蛋白水平显著相关。在组织样本中，观察到 ER-α 和 TIF2、AIB1、P/CAF 以及 N-CoR 之间，以及 ER-β 和 AIB1 以及 CBP 之间的表达水平存在显著相关性。在细胞系中，也观察到 ER-α 和 ER-β 之间以及 ER-β 和 CBP 之间存在显著相关性。导管内癌中 ER-α、TIF2 和 CBP 的表达水平显著高于正常乳腺组织。此外，导管内癌中 ER-α 和 N-CoR 的表达水平显著高于浸润性导管癌。这些发现提示 ER-α 与辅因子之间以及 ER-β 与辅因子之间的表达水平呈正相关，从正常乳腺组织发展为导管内癌过程中 ER-α 和辅因子的表达水平上调，而在乳腺癌进展过程中其表达水平下降。
