c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-lot dependent
c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-lot dependent
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DOI：
10.1158/1078-0432.ccr-04-1068
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发表时间：
2004-12-01
影响因子：
11.5
通讯作者：
Sivridis, E
中科院分区：
文献类型：
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作者：
Giatromanolaki, A;Koukourakis, MI;Sivridis, E
c-erbB-2阳性乳腺癌是高度侵袭性的肿瘤。关于乳腺细胞系的体外数据显示，c-erbB-2增强了缺氧诱导因子-Ia（HIF 1 α）产生的翻译效率（Laughner等人，Mol Cell Biol 2001;21：3995-4005）。我们研究了这一观察结果的临床相关性，以评估c-erbB-2表达是否与HIFl α表达、血管生成和预后相关。对一系列180例c-erbB-2状态已知的乳腺癌（90例c-erbB-2阳性和90例c-erbB-2阴性癌）进行了HIFl α和CD 31上皮细胞抗原的免疫组织化学染色。c-erbB-2阳性与HIFl α蛋白表达和高血管生成明显相关。然而，只有同时表达c-erbB-2和HIFl α的病例预后才降低。如果c-erbB-2在人体中的激活导致HIFl α的过度表达而不依赖于缺氧条件，如实验研究中所发生的那样，这种相互作用可能代表了赋予c-erbB-2阳性乳腺肿瘤临床侵袭性的主要途径。
c-erbB-2-positive breast carcinomas are highly aggressive tumors. In vitro data on breast cell lines showed that c-erbB-2 enhanced translational efficiency of hypoxia inducible factor-lalpha (HIFlalpha) production (Laughner et aL, Mol Cell Biol 2001;21:3995-4005). We investigated the clinical correlate of this observation to assess whether c-erbB-2 expression was related to HIFlalpha expression, angiogenesis, and prognosis. A series of 180 breast carcinomas of known cerbB-2 status (90 c-erbB-2-positive and 90 c-erbB-2-negative carcinomas) were stained inummohistochemically for HIFlalpha and CD31 enclothelial cell antigen. c-erbB-2 positivity was clearly related to HIFlalpha protein expression and high angiogenesis. However, prognosis was decreased only In cases with simultaneous c-erbB-2 and HIFlalpha expression. If activation of c-erbB-2 in humans results in overexpression of HIFlalpha independently of conditions of hypoxia, as occur in experimental studies, this interaction may represent a main pathway conferring clinical aggressiveness to c-erbB-2positive breast tumors.