Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients.
Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients.
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DOI：
10.1038/sj.bjc.6600126
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发表时间：
2002-02-12
影响因子：
8.8
通讯作者：
Stal, O
中科院分区：
文献类型：
--
作者：
Perez-Tenorio, G;Stal, O
Akt/PKB是一种丝氨酸/苏氨酸蛋白激酶，与酪氨酸激酶受体相关，调节细胞周期进程、凋亡和生长因子介导的细胞存活。该蛋白是erbB-2的下游效应物，在体外乳腺癌进展和耐药性中具有意义。我们的目的是研究Akt-1在乳腺癌患者中的作用，通过确定表达（Akt-1）和/或激活（pAkt）是否与预后标志物和生存相关。流式细胞术和免疫组化检测erbB-2、heregulin β1和Bcl-2的表达。该研究包括93名年龄<50岁的患者，他们接受了他莫昔芬和/或戈舍瑞林治疗。我们发现pAkt与较低的S期分数（P=0.001）和表达heregulin β1的基质细胞的存在（P=0.017）相关。Akt-1和pAkt与其他因素无关。肿瘤细胞源性heregulin β1主要表达于雌激素受体阴性（P=0.026）和淋巴结阴性（P=0.005）病例。生存分析显示，pAkt阳性患者更容易复发远处转移，独立于S期分数和淋巴结状态（多变量分析; P=0.004）。结果表明，Akt的激活可能与乳腺癌的预后相关。英国癌症杂志（2002）86，540-545。DOI：10.1038/sj/bjc/6600126 www.bjcancer.com © 2002英国癌症研究中心
Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors. The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin β1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry. This study comprised 93 patients, aged <50 who were treated with tamoxifen and/or goserelin. We found that pAkt was associated with lower S-phase fraction (P=0.001) and the presence of heregulin β1-expressing stromal cells (P=0.017). Neither Akt-1 nor pAkt was related with other factors. Tumour cells-derived heregulin β1 was found mainly in oestrogen receptor negative (P=0.026) and node negative (P=0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant metastasis, independently of S-phase fraction and nodal status (multivariate analysis; P=0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer. British Journal of Cancer (2002) 86, 540–545. DOI: 10.1038/sj/bjc/6600126 www.bjcancer.com © 2002 Cancer Research UK