Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma.
- Author:
Cong-qing JIANG
1
;
Li-fang FAN
;
Zhi-su LIU
;
Qun QIAN
;
Dong XIA
;
Lu-ming DIAO
;
Yue-ming HE
;
Zhong-li AI
Author Information
- Publication Type:Journal Article
- MeSH: Adenocarcinoma; blood supply; pathology; Adult; Aged; Aged, 80 and over; Cell Line, Tumor; Colorectal Neoplasms; blood supply; pathology; DNA-Binding Proteins; analysis; genetics; physiology; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Middle Aged; Neovascularization, Pathologic; etiology; Nuclear Proteins; analysis; genetics; physiology; RNA, Messenger; analysis; Transcription Factors; analysis; genetics; physiology; Vascular Endothelial Growth Factor A; analysis; physiology
- From: Chinese Medical Journal 2004;117(10):1541-1546
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDHypoxia-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-1alpha and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1alpha and VEGF play important roles in tumor angiogenesis.
METHODSHIF-1alpha mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1alpha 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-1alpha protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD34 immunostaining in colorectal carcinomas.
RESULTSOptical density values representing HIF-1alpha 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-1alpha 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-1alpha mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes' stages (P < 0.05). HIF-1alpha mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P < 0.01). HIF-1alpha protein expression correlated significantly with VEGF protein expression and MVD.
CONCLUSIONSHypoxia induces the expression of HIF-1alpha and VEGF in colorectal adenocarcinomas. HIF-1alpha may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.