IDENTIFICATION AND LOCALIZATION OF ALTERNATELY SPLICED MESSENGER-RNAS FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR IN HUMAN UTERUS AND ESTROGEN REGULATION IN ENDOMETRIAL CARCINOMA CELL-LINES
IDENTIFICATION AND LOCALIZATION OF ALTERNATELY SPLICED MESSENGER-RNAS FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR IN HUMAN UTERUS AND ESTROGEN REGULATION IN ENDOMETRIAL CARCINOMA CELL-LINES
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DOI：
10.1095/biolreprod48.5.1120
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发表时间：
1993-05-01
影响因子：
3.6
通讯作者：
SMITH, SK
中科院分区：
文献类型：
--
作者：
CHARNOCKJONES, DS;SHARKEY, AM;SMITH, SK
人月经后子宫内膜的修复和着床前的准备涉及深刻的血管生成变化。血管内皮细胞生长因子（VEGF）是最近发现的具有显著血管生成特性的生长因子。在人子宫内膜和子宫肌层中鉴定出4种编码VEGF的mRNA。所有物种都存在于整个月经周期。两个物种，VEGF 165和VEGF 121，存在于外周血白细胞，表明组织特异性剪接的其他两个VEGF转录。原位杂交的mRNA编码的血管内皮生长因子不限于血管平滑肌，但存在于上皮细胞和基质细胞的子宫内膜在整个周期，并在周期的过程中的分布发生变化。子宫内膜癌细胞系石川、HEC 1-A和HEC 1-B表达所有四种VEGF。在HEC 1-A细胞中，雌二醇以剂量和时间依赖性方式增加编码VEGF的mRNA的稳态水平。来自这些细胞的条件培养基具有血管生成活性，其通过肝素亲和柱被耗尽。尽管先前报道在HEC 1-A和HEC 1-B细胞中鉴定了免疫反应性碱性FGF，但没有细胞系显示酸性或碱性成纤维细胞生长因子（FGF）的mRNA。这些发现表明，VEGF，而不是FGF，是这些细胞分泌的主要血管生成生长因子，并且人子宫内膜表达分泌的血管生成生长因子，其表达位点在月经周期中发生变化。
Repair of human endometrium after menstruation and preparation of the endometrium for implantation involves profound angiogenic changes. Vascular endothelial cell growth factor (VEGF) is a recently identified growth factor with significant angiogenic properties. Four species of mRNA encoding VEGFs were identified in human endometrium and myometrium. All species were present throughout the menstrual cycle. Two species, VEGF165 and VEGF121, were present in peripheral leukocytes, indicating tissue-specific splicing of the two other VEGF transcripts. In situ hybridization of mRNA encoding VEGF was not restricted to vascular smooth muscle but was present in epithelial and stromal cells of endometrium throughout the cycle, and the distribution changed during the course of the cycle. All four species of VEGF were expressed by the endometrial carcinoma cell lines Ishikawa, HEC 1-A, and HEC 1-B. Estradiol increased steady-state levels of mRNA encoding VEGF in a dose- and time-dependent manner in HEC 1-A cells. Conditioned medium from these cells possessed angiogenic activity that was depleted by passage through a heparin affinity column. None of the cell lines demonstrated mRNA for acidic or basic fibroblast growth factor (FGF), despite previous reports of the identification of immunoreactive basic FGF in HEC 1-A and HEC 1-B cells. These findings show that VEGFs, not FGFs, are the principal angiogenic growth factors secreted by these cells and that human endometrium expresses a secreted angiogenic growth factor whose site of expression changes during the menstrual cycle.