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Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma

江从庆 樊利芳 刘志苏 钱群 夏东 刁路明 何跃明 艾中立

中华医学杂志(英文版)Issue(10):1541-1546,6.
中华医学杂志(英文版)Issue(10):1541-1546,6.

Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma

Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma

江从庆 1樊利芳 2刘志苏 1钱群 1夏东 2刁路明 2何跃明 1艾中立1

作者信息

  • 1. Department of Colorectal Surgery,Zhongnan Hospital of Wuhan University,Wuhan 430071,China
  • 2. Department of Pathology,Medical College of Wuhan University,Wuhan 430071,China
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摘要

Abstract

Background Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1α and VEGF play important roles in tumor angiogenesis. Methods HIF-1α mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1α and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1α protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD34 immunostaining in colorectal carcinomas. Results Optical density values representing HIF-1α mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P<0.05) or in hypoxic conditions but treated with genistein (P<0.05). The levels of HIF-1α and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P<0.01, P<0.05, respectively) and hypoxia/genistein group (P<0.01, P<0.05, respectively). The positive expression rates of HIF-1α mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes' stages (P<0.05). HIF-1α mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P<0.01). HIF-1α protein expression correlated significantly with VEGF protein expression and MVD.Conclusions Hypoxia induces the expression of HIF-1α and VEGF in colorectal adenocarcinomas. HIF-1α may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.

关键词

colorectal tumor/hypoxia-inducible factor-1/vascular endothelial growth factor/angiogenesis/microvessel density

Key words

colorectal tumor/hypoxia-inducible factor-1/vascular endothelial growth factor/angiogenesis/microvessel density

分类

医药卫生

引用本文复制引用

江从庆,樊利芳,刘志苏,钱群,夏东,刁路明,何跃明,艾中立..Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma[J].中华医学杂志(英文版),2004,(10):1541-1546,6.

基金项目

This study was supported by the Fund for Key Technologies R and D Programme of Hubei Province (No.2003AA301CO3). (No.2003AA301CO3)

中华医学杂志(英文版)

OACSTPCDMEDLINESCI

0366-6999

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