Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1
Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1
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DOI：
10.1136/jcp.2004.016733
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发表时间：
2004-10-01
影响因子：
3.4
通讯作者：
Young, LS
中科院分区：
文献类型：
--
作者：
Fleming, FJ;Myers, E;Young, LS
背景：在人类乳腺癌中，生长因子受体HER 2与疾病进展和对内分泌治疗的抵抗相关。生长因子诱导的丝裂原活化蛋白激酶（MAPK）活性不仅可以磷酸化雌激素受体，还可以磷酸化雌激素受体的辅激活蛋白AIB 1和SRC-1。为了确定HER 2阳性患者对内分泌治疗的不敏感性是否与共激活蛋白的表达增强、HER 2转录调节因子PEA 3和共调节蛋白AIB 1和SRC-1的表达相关，方法：PEA 3，AIB 1和SRC-1蛋白表达在70个原发性乳腺肿瘤的已知HER 2状态（HER 2阳性，n=35）和6个减少乳房成形术使用免疫组化进行了评估。使用免疫荧光测定PEA 3与AIB 1和SRC-1的共定位。PEA 3、AIB 1和SRC-1的表达与临床病理参数相关。结果：在原发性乳腺肿瘤中，PEA 3、AIB 1和SRC-1的表达与HER 2状态相关（分别为p=0.0486、p=0.0444和p=0.0012）。在HER 2阳性人群中，PEA 3表达与SRC-1相关（p=0.0354），单变量分析显示PEA 3和SRC-1均与复发显著相关（p=0.0345; p
Background: In human breast cancer, the growth factor receptor HER2 is associated with disease progression and resistance to endocrine treatment. Growth factor induced mitogen activated protein kinase activity can phosphorylate not only the oestrogen receptor, but also its coactivator proteins AIB1 and SRC-1.Aim: To determine whether insensitivity to endocrine treatment in HER2 positive patients is associated with enhanced expression of coactivator proteins, expression of the HER2 transcriptional regulator, PEA3, and coregulatory proteins, AIB1 and SRC-1, was assessed in a cohort of patients with breast cancer of known HER2 status.Methods: PEA3, AIB1, and SRC-1 protein expression in 70 primary breast tumours of known HER2 status (HER2 positive, n=35) and six reduction mammoplasties was assessed using immunohistochemistry. Colocalisation of PEA3 with AIB1 and SRC-1 was determined using immunofluorescence. Expression of PEA3, AIB1, and SRC-1 was correlated with clinicopathological parameters.Results: In primary breast tumours expression of PEA3, AIB1, and SRC-1 was associated with HER2 status (p=0.0486, p=0.0444, and p=0.0012, respectively). In the HER2 positive population, PEA3 expression was associated with SRC-1 (p=0.0354), and both PEA3 and SRC-1 were significantly associated with recurrence on univariate analysis (p=0.0345; p