Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients
Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients
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DOI：
10.1002/ijc.21358
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发表时间：
2006-01-15
影响因子：
6.4
通讯作者：
Maehara, Y
中科院分区：
文献类型：
--
作者：
Tokunaga, E;Kimura, Y;Maehara, Y
Akt/PKB是一种丝氨酸/苏氨酸激酶，当细胞暴露于不同的凋亡刺激时，其在存活中起重要作用。Akt/PKB异常激活与乳腺癌预后不良及对内分泌治疗和化疗耐药有关。AKt信号通路目前作为有效治疗策略的新靶点引起了相当大的关注。因此，我们研究了Akt激活与临床病理变量（包括激素受体和HER 2/neu状态）之间的关系。从252名患者获得的乳腺癌组织用于本研究。我们通过免疫组化评估磷酸化Akt（pAkt）在Ser-473的表达来评估Akt激活。pAkt阳性表达84例（33.3%）。pAkt与HER 2/neu过表达显著相关（p < 0.0001）。pAkt与PR表达呈负相关（p = 0.0321）;然而，pAkt与ER表达无相关性。生存分析显示，pAkt阳性与术后激素治疗病例的无病生存率相关;然而，在未接受激素治疗的病例中，无相关性。我们的研究结果表明，Akt激活诱导接受辅助激素治疗的患者预后不良。这一发现表明，抑制Akt信号通路可能会增加激素治疗的疗效，并改善接受辅助激素治疗的患者的预后。(c)2005 Wiley-Liss，Inc.
Akt/PKB is a serine/threonine kinase that plays an important role in survival when cells are exposed to different apoptotic stimuli. Aberrant activation of Akt/PKB in breast carcinoma is associated with poor prognosis and resistance to endocrine therapy and chemotherapy. The AKt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Breast cancer tissues obtained from 252 patients were utilized for this study. We evaluated AKt activation by immunohistochemical assessment of the expression of phosphorylated Akt (pAkt) at Ser-473. Eighty-four cases (33.3%) were diagnosed as positive for pAkt expression. pAkt was significantly associated with HER2/neu overexpression (p < 0.0001). There was an inverse correlation between pAkt and PR expression (p = 0.0321); however, there was no association between pAkt and ER expression. Survival analysis showed that pAkt positivity was associated with poor disease-free survival in cases with postoperative hormone therapy; however, there was no association in cases without hormone therapy. Our results indicate that Akt activation induced poor prognosis in patients who received adjuvant hormone therapy. This finding suggests that inhibition of the Akt signaling pathway may increase the efficacy of hormone therapy and improve the prognosis of patients who receive adjuvant hormone therapy. (c) 2005 Wiley-Liss, Inc.