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

1.雌激素受体α（ERα）在乳腺癌细胞系中的转录调控我们用TATA荧光素酶法分析了SRC-1、AIB 1、PCAF和CARM 1等ERα辅因子在转化的COS 7细胞中的转录活性。AIB 1的ER α转录活性强于SRC-1、PCAF和CARM 1。AIB 1是SRC-1家族核受体辅激活因子的成员，与类固醇激素受体相互作用，增强配体依赖性.乳腺癌AIB 1基因的扩增我们分析了124个原发性乳腺癌DNA，用EcoRI消化，并用1.27-kb cDNA探针固定在Southern印迹膜上。在124例乳腺肿瘤中的2例（1.6%）中观察到扩增。病例1扩增水平为3倍。例2杂交带上移，扩增倍数为5倍。这种扩增非常罕见，并且被认为对乳腺癌的激素发展并不重要。AIB1 ov ...更多信息 应用免疫组化法检测115例乳腺癌组织中AIB 1蛋白的表达。阳性染色主要分布于细胞核、细胞质及细胞核与细胞质。以核染色为阳性时，阳性率为16%（18/115）。AIB 1的阳性表达与ER α状态相关（P=0.021）。在接受内分泌治疗的患者中，5例AIB 1阳性、ER阳性患者中有4例对内分泌治疗有反应，而16例AIB 1阴性、ER阳性患者中只有4例对内分泌治疗有反应（P=0.047）。这意味着AIB 1的核表达被认为是乳腺癌内分泌治疗的预测因子.乳腺癌中野生型ER β表达的临床意义88例乳腺癌中ER β阳性表达52例（59%）。ER β染色与ER α状态相关（P=0.02）。ER β阳性者的无病生存率明显高于阴性者（Logrank检验：P=0.017）。我们的数据表明，野生型ERβ蛋白的表达可以作为一个良好的乳腺癌预后指标的可能性。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