TRPS1 expression promotes angiogenesis and affects VEGFA expression in breast cancer

TRPS1 expression promotes angiogenesis and affects VEGFA expression in breast cancer
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TRPS1表达促进乳腺癌血管生成并影响VEGFA表达

DOI:
10.1177/1535370214523904
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发表时间:
2014-04-01
影响因子:
3.2
通讯作者:
Zhou, Gengyin
Zhou, Gengyin
中科院分区:
医学4区
文献类型:
--
作者:
Hu, Jing;Su, Peng;Zhou, Gengyin

文献摘要

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血管生成是乳腺癌恶性过程的标志,其中血管内皮生长因子A(VEGFA)起着重要作用。Trichorhinophalangeal syndrome type 1(TRPS1)是一种GATA型转录因子,与Trichorhinophalangeal syndrome type 1有关。为探讨TRPS1在乳腺癌血管生成中的作用,我们采用免疫组织化学方法检测了117例石蜡包埋乳腺组织中TRPS1和微血管密度(MVD)标志物CD31的表达。TRPS1表达与CD31呈正相关。我们进一步研究了TRPS 1是否诱导人脐静脉内皮细胞(HUVEC)迁移和乳腺癌细胞表达VEGFA。TRPS1的过表达诱导HUVEC迁移显著增加,同时转染细胞中VEGFA上调。与此相反,TRPS1的敲低降低了HUVEC迁移的诱导,并显着下调VEGFA的表达。此外,内源性TRPS1存在于VEGFA启动子中,通过染色质免疫沉淀测定。总之,这项研究表明,TRPS1促进血管生成并影响乳腺癌中VEGFA的表达。
Angiogenesis is a hallmark of the malignant process in breast cancer in which vascular endothelial growth factor A (VEGFA) plays an important role. Trichorhinophalangeal syndrome type 1 (TRPS1) is a GATA-type transcription factor and is involved in trichorhinophalangeal syndrome type 1. To investigate the role of TRPS1 in breast cancer angiogenesis, we analyzed the expression of TRPS1 and microvessel density (MVD) marker CD31 by immunohistochemistry in 117 paraffin-embedded breast tissues. TRPS1 expression was positively correlated with CD31. We further investigated whether TRPS1induces human umbilical vein endothelial cell (HUVEC) migration and VEGFA expression of breast cancer cells. The over-expression of TRPS1 induced a significant increase in HUVEC migration accompanied by VEGFA up-regulation in transfected cells. In contrast, knockdown of TRPS1 decreased the induction of HUVEC migration and significantly down-regulated VEGFA expression. Furthermore, endogenous TRPS1 was present in the VEGFA promoter, as determined by chromatin immunoprecipitation assay. Taken together, this study showed that TRPS1 promotes angiogenesis and affects VEGFA expression in breast cancer.