Stanniocalcin-1 promotes tumor angiogenesis through up-regulation of VEGF in gastric cancer cells.

Stanniocalcin-1 promotes tumor angiogenesis through up-regulation of VEGF in gastric cancer cells.
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Stanniocalcin-1通过上调胃癌细胞中的VEGF促进肿瘤血管生成

DOI:
10.1186/1423-0127-18-39
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发表时间:
2011-06-14
影响因子:
11
通讯作者:
Hou YY
Hou YY
中科院分区:
医学1区
文献类型:
--
作者:
He LF;Wang TT;Gao QY;Zhao GF;Huang YH;Yu LK;Hou YY

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Stanniocalcin-1(STC-1)在包括胃癌在内的多种癌症中表达上调。有证据表明,STC-1与肿瘤的发生和血管生成过程有关。方法构建高表达STC-1的BGC/STC细胞和低表达STC-1的BGC/shSTC细胞,观察STC-1在体内外对移植瘤生长和血管生成的影响。用ELISA法检测培养上清液中血管内皮生长因子(VEGF)的表达。用中和抗体抑制培养上清液中血管内皮生长因子的表达。Western blotting检测经STC-1蛋白处理的BGC中磷酸化的PKCβII、磷酸化的ERK1/2和磷酸化的P38的表达。用中和抗体抑制培养上清液中血管内皮生长因子的表达,可明显抑制STC-1诱导的血管生成。结论STC-1通过激活PKC、βII和ERK1/2途径促进血管内皮细胞生长因子的表达。结论STC-1通过激活PKC、βII和ERK1/2途径促进血管内皮生长因子的表达。血管内皮生长因子随后促进肿瘤血管生成,进而促进胃肿瘤的生长。
BackgroundStanniocalcin-1(STC-1) is up-regulated in several cancers including gastric cancer. Evidences suggest that STC-1 is associated with carcinogenesis and angiogenic process. However, it is unclear on the exact role for STC-1 in inducing angiogenesis and tumorigeneisis.MethodBGC/STC cells (high-expression of STC-1) and BGC/shSTC cells (low- expression of STC-1) were constructed to investigate the effect of STC-1 on the xenograft tumor growth and angiogenesisin vitroandin vivo. ELISA assay was used to detect the expression of vascular endothelial growth factor (VEGF) in the supernatants. Neutralizing antibody was used to inhibit VEGF expression in supernatants. The expression of phosphorylated -PKCβII, phosphorylated -ERK1/2 and phosphorylated -P38 in the BGC treated with STC-1protein was detected by western blot.ResultsSTC-1 could promote angiogenesisin vitroandin vivo, and the angiogenesis was consistent with VEGF expressionin vitro. Inhibition of VEGF expression in supernatants with neutralizing antibody markedly abolished angiogenesis induced by STC-1in vitro. The process of STC-1-regulated VEGF expression was mediated via PKCβII and ERK1/2.ConclusionsSTC-1 promotes the expression of VEGF depended on the activation of PKCβII and ERK1/2 pathways. VEGF subsequently enhances tumor angiogenesis which in turn promotes the gastric tumor growth.
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