Analysis of the Estrogen Receptor α cofactors with reference to Hormone Dependency of Breast Cancer

1. 雌激素受体α(estrogen receptor α, ERα)在乳腺癌细胞系中的转录调控采用TATA荧光素酶法分析了转化的COS7细胞中各种ERα辅助因子SRC-1、AIB1、PCAF和CARM1的转录活性。AIB1的ER α转录活性强于SRC-1、PCAF和CARM1。AIB1是SRC-1家族核受体共激活因子的一员，可与类固醇激素受体相互作用，增强配体依赖性。我们分析了124个用EcoRI酶切的原发性乳腺癌dna，并用1.27 kb cDNA探针固定在Southern blotting膜上。124例乳腺肿瘤中有2例（1.6%）存在扩增。病例1的扩增水平为3倍。病例2杂交带上移，扩增水平为5倍。这种放大是非常罕见的，并且被认为对乳腺癌的激素发展并不重要。我们对115例乳腺癌患者进行了AIB1蛋白的免疫组化检测。细胞核、细胞质及二者均呈阳性染色。核染色为阳性时，阳性率为16%（18/115）。AIB1阳性与ER α状态相关（P=0.021）。在接受内分泌治疗的患者中，5例AIB1阳性和ER阳性患者中有4例对内分泌治疗有应答，而16例AIB1阴性和ER阳性患者中只有4例对内分泌治疗有应答（P=0.047）。这意味着AIB1的核表达被认为是乳腺癌内分泌治疗的预测因素。野生型ER β在乳腺癌中表达的临床价值。88例乳腺癌中有52例（59%）出现ER β阳性染色。ER β染色与ER α状态相关（P=0.02）。ER β阳性患者预后优于阴性患者无病生存率（Logrank检验：P=0.017）。我们的数据表明，野生型ERβ蛋白表达可能被用作乳腺癌的良好预后指标。少

1. Transcriptional regulation of the estrogen receptor α(ERα) in breast cancer cell linesWe analyzed the transcriptional activity of the various kinds ERα cofactors, such as SRC-1, AIB1, PCAF, and CARM1 using TATA luciferase assay in the transformed COS7 cells. The ER α transcriptional activity of AIB1 was stronger than those of SRC-1, PCAF, and CARM1. AIB1 is a member of the SRC-1 family nuclear receptor coactivators, which interact with steroid hormone receptors to enhance ligand-dependent manner.2. Gene amplification of AIB1 in breast cancerWe analyzed 124 primary breast cancer DNAs digested with EcoRI and immobilized on Southern blotting membranes with a 1.27-kb cDNA probe. Amplification was observed in two of 124(1.6%)breast tumors. Amplification level of case 1 was 3-fold. Hybridization band of case 2 was upper-shifted and its amplification level was 5-fold. This amplification was qite rare and was thought to be unimportant for the hormonal development of breast cancer.3. AIB1 ov … More erexpression in breast cancerWe performed immunohistochemical detection of AIB1 protein in 115 cases with breast cancer. The positive staining was showed in the nucleus, cytoplasm and both of them. When the nuclear staining was evaluate as positive, the positive rate was 16%(18/115). The positivity of AIB1 was correlated with ER α status(P=0.021). In the patents treated by endocrine therapy, 4 of 5 patient with positive AIB1 and positive ER were responsive for endocrine therapy, whereas only 4 of 16 patients with negative AIB1 and positive ER were responsive(P=0.047). This means that the nuclear expression of AIB1 was thought to be predictive factors for endocrine therapy in breast cancer.4. Clinical value of the wild-type ER β expression in breast cancer.ER β positive staining was seen in 52(59%)of 88 breast cancers. ER β staining was correlated with ER α status(P=0.02). ER β positive cases showed a better prognosis than negative cases in disease -free survival rate(Logrank test : P=0.017). Our data demonstrated the possibility that the wild-type ERβ protein expression could be used as a good prognostic indicator for breast cancer. Less