Regulation of vascular endothelial cell growth factor expression in mouse mammary tumor cells by the EP2 subtype of the prostaglandin E2 receptor
Regulation of vascular endothelial cell growth factor expression in mouse mammary tumor cells by the EP2 subtype of the prostaglandin E2 receptor
复制标题
DOI：
10.1016/j.prostaglandins.2004.12.001
复制
发表时间：
2005-05-01
影响因子：
2.9
通讯作者：
Hla, T
中科院分区：
文献类型：
--
作者：
Chang, SH;Liu, CH;Hla, T
前列腺素E-2（PGE（2））是乳腺中环氧合酶途径的主要代谢产物，在乳腺肿瘤进展过程中诱导血管生成。为了更好地定义所涉及的分子机制，我们研究了从MMTV-COX-2（考克斯-2）转基因小鼠中分离的乳腺肿瘤细胞系中PGE2的G蛋白偶联受体（GPCR）的作用。PGE2受体EP2亚型的表达与肿瘤发生表型和诱导血管内皮生长因子（VEGF）的能力相关。通过腺病毒转导EP 2到EP 2缺失细胞中的过表达导致对PGE（2）和EP 2受体激动剂CAY 10399的响应的VEGF表达的诱导。EP 2受体诱导VEGF不需要缺氧诱导因子（HIF）-1 α途径、MAP激酶途径或磷酸肌醇-3-激酶/Akt途径，但需要cAMP/蛋白激酶A途径。这些结果表明，EP 2受体是PGE 2介导的小鼠乳腺肿瘤细胞VEGF诱导的关键元件。(c)2005年爱思唯尔公司All rights reserved.
Prostaglandin E-2 (PGE(2)), a major metabolite of the cyclooxygenase pathway in the mammary gland, induces angiogenesis during mammary tumor progression. To better define the molecular mechanisms involved, we examined the role of the G protein-coupled receptors (GPCR) for PGE2 in mammary tumor cell lines isolated from MMTV-cyclooxygenase-2 (COX-2) transgenic mice. Expression of the EP2 subtype of the PGE2 receptor was correlated with the tumorigenic phenotype and the ability to induce vascular endothelial growth factor (VEGF). Overexpression of EP2 by adenoviral transduction into EP2-null cells resulted in the induction of VEGF expression in response to PGE(2) and CAY10399, an EP2 receptor agonist. The induction of VEGF by the EP2 receptor did not require the hypoxia inducible factor (HIF)-1 alpha pathway, MAP kinase pathway, or phosphoinositide-3-kinase/Akt pathway, but required the cAMP/protein kinase A pathway. These results suggest that EP2 receptor is a critical element for PGE2 mediated VEGF induction in mouse mammary tumor cells. (c) 2005 Elsevier Inc. All rights reserved.