Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on α6β1 integrin in breast carcinoma cells
Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on α6β1 integrin in breast carcinoma cells
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DOI：
10.1158/0008-5472.can-04-0347
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发表时间：
2004-07-15
期刊：
影响因子：
11.2
通讯作者：
Mercurio, AM
中科院分区：
文献类型：
--
作者：
Chung, J;Yoon, S;Mercurio, AM
α 6 β 1整合素与乳腺癌的进展有关，但其机制仍不清楚。经工程改造为α 6 β 1表达缺陷的MDA-MB-435细胞形成高度凋亡且不能转移的原发性肿瘤，尽管它们在标准培养条件下在体外没有表现出凋亡增加。基于这一假设，即α 6 β 1是必要的这些细胞在肿瘤微环境中的生存，我们在这里报告，缺氧保护这些细胞从血清剥夺诱导的细胞凋亡和缺氧介导的保护需要α 6 β 1的表达。我们研究了α 6 β 1对血管内皮生长因子（VEGF）表达的影响，因为自分泌VEGF是缺氧条件下血清剥夺细胞存活所必需的。所获得的结果表明，α 6 β 1是VEGF表达所必需的，因为缺氧激活HIF-1和刺激MDA-MB-435细胞中VEGF转录的能力依赖于α 6 β 1表达，其机制涉及蛋白激酶C-α。
The alpha6beta1 integrin has been implicated in breast carcinoma progression, but the mechanisms involved remain elusive. MDA-MB-435 cell engineered to be deficient in alpha6beta1 expression form primary tumors that are highly apoptotic and unable to metastasize, although they exhibit no increased apoptosis in vitro under standard culture conditions. Based on the hypothesis that alpha6beta1 is necessary for the survival of these cells in the tumor microenvironment, we report here that hypoxia protects these cell from apoptosis induced by serum deprivation and that hypoxia-mediated protection requires alpha6beta1 expression. We investigated the influence of alpha6beta1 on vascular endothelial growth factor (VEGF) expression because autocrine VEGF is necessary for the survival of serum-deprived cells in hypoxia. The results obtained indicate that alpha6beta1 is necessary for VEGF expression because the ability of hypoxia to activate HIF-1 and to stimulate VEGF transcription in MDA-MB-435 cells is dependent on alpha6beta1 expression by a mechanism that involves protein kinase C-alpha.