催乳素通过早期生长反应因子-1诱导血管内皮生长因子的表达。

Prolactin-induced expression of vascular endothelial growth factor via Egr-1.

作者信息

Goldhar Anita S, Vonderhaar Barbara K, Trott Josephine F, Hovey Russell C

机构信息

Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1402, USA.

出版信息

Mol Cell Endocrinol. 2005 Mar 31;232(1-2):9-19. doi: 10.1016/j.mce.2005.01.005.

DOI:10.1016/j.mce.2005.01.005

PMID:15737464

Abstract

Angiogenesis is a dynamic process regulated by both local and systemic factors. Among these is vascular endothelial growth factor (VEGF), a potent effector of angiogenesis and vascular permeability. Previously we showed that VEGF is temporally and spatially regulated in the mouse mammary gland during development and lactation. Given the functions of prolactin (PRL) during these stages and the supporting role of the vasculature, we investigated the regulation of VEGF by PRL. Treatment of HC11 mouse mammary epithelial and Nb2 rat lymphoma cells with PRL induced VEGF expression. Deletion and mutation analysis identified a GC-rich region in the proximal region of the VEGF promoter that constitutively bound Sp1 and PRL-induced Egr-1. These sites conferred PRL-responsiveness leading to increased VEGF transcription. The induction of VEGF by PRL was PRL receptor-, Jak2- and MAP kinase kinase-dependent. Our results indicate that PRL induces VEGF expression through Egr-1, and implicates VEGF as an intermediary of PRL-regulated angiogenesis.

摘要

血管生成是一个受局部和全身因素调节的动态过程。其中包括血管内皮生长因子（VEGF），它是血管生成和血管通透性的强效效应因子。此前我们发现，在小鼠乳腺发育和泌乳过程中，VEGF在时间和空间上受到调控。鉴于催乳素（PRL）在这些阶段的功能以及脉管系统的支持作用，我们研究了PRL对VEGF的调控。用PRL处理HC11小鼠乳腺上皮细胞和Nb2大鼠淋巴瘤细胞可诱导VEGF表达。缺失和突变分析确定了VEGF启动子近端区域一个富含GC的区域，该区域组成性结合Sp1和PRL诱导的Egr-1。这些位点赋予PRL反应性，导致VEGF转录增加。PRL对VEGF的诱导依赖于PRL受体、Jak2和丝裂原活化蛋白激酶激酶。我们的结果表明，PRL通过Egr-1诱导VEGF表达，并提示VEGF是PRL调节血管生成的中介物。