Endocrine glands-derived vascular endothelial growth factor protects pancreatic cancer cells from apoptosis via upregulation of the myeloid cell leukemia-1 protein.
Endocrine glands-derived vascular endothelial growth factor protects pancreatic cancer cells from apoptosis via upregulation of the myeloid cell leukemia-1 protein.
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DOI：
10.1016/j.bbrc.2009.05.149
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发表时间：
2009-08
影响因子：
3.1
通讯作者：
L. Ren;Qingfang Li;F. Xiao;Jun Yan;Yuefeng Yang;Li-Sheng Wang;Xiaozhong Guo;Hua Wang
中科院分区：
文献类型：
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作者：
L. Ren;Qingfang Li;F. Xiao;Jun Yan;Yuefeng Yang;Li-Sheng Wang;Xiaozhong Guo;Hua Wang
内分泌腺源性血管内皮生长因子(EG-VEGF，又称Prok1)是一种选择性作用于内分泌腺内皮细胞的新型细胞因子，近年来被报道参与调节肿瘤细胞的生长和存活。然而，它在调节胰腺癌进展中的作用仍不清楚。本研究旨在探讨EG-VEGF对胰腺癌细胞凋亡的抑制作用及其机制。逆转录-聚合酶链式反应(RT-PCR)发现胰腺癌细胞系Mia Paca II细胞同时表达EG-VEGF(Prok1)及其受体的mRNAs。EG-VEGF通过上调髓系细胞白血病-1(Mcl-1)来保护胰腺癌细胞免于凋亡，Mcl-1是bcl2家族的一种抗凋亡蛋白。EG-VEGF诱导胰腺癌细胞MAPK、STAT3和AKT的快速磷酸化，参与Mcl-1表达的上调。EG-VEGF(Prok1)通过G蛋白偶联受体(GPR)诱导的多条信号通路的激活，保护Mia Paca II细胞免于凋亡，有望成为胰腺癌治疗的新靶点。
Endocrine glands-derived vascular endothelial growth factor (EG-VEGF, also termed as Prok1)—a novel cytokine that selectively acts on the endothelial cells of endocrine glands—was recently reported to be involved in the regulation of tumor cell growth and survival. However, its roles in the regulation of pancreatic cancer progression remain unclear. In this report, we investigated the suppressive effects of EG-VEGF on pancreatic cancer cell apoptosis and the relevant mechanisms. By using reverse-transcriptase polymerase chain reaction (RT-PCR) we found that the Mia PaCa II cells of the pancreatic cancer cell line express the mRNAs of both EG-VEGF (Prok1) and its receptors. EG-VEGF protects pancreatic cancer cells from apoptosis through upregulation of myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic protein of the bcl-2 family. Treatment of pancreatic cancer cells with EG-VEGF results in the rapid phosphorylation of mitogen-activated protein kinase (MAPK), STAT3, and AKT, which are involved in the upregulation of Mcl-1 expression. EG-VEGF (Prok1) protects Mia PaCa II cells from apoptosis through G protein-coupled receptor (GPR)-induced activation of multiple signal pathways, and hence can be a novel target for pancreatic cancer therapy.