Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 1541-1546, 2004.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-291884
Responsible library:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>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-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.</p><p><b>METHODS</b>HIF-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.</p><p><b>RESULTS</b>Optical 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.</p><p><b>CONCLUSIONS</b>Hypoxia 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.</p>
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Physiology
/
Transcription Factors
/
RNA, Messenger
/
Nuclear Proteins
/
Colorectal Neoplasms
/
Adenocarcinoma
/
Cell Line, Tumor
/
Vascular Endothelial Growth Factor A
/
DNA-Binding Proteins
Limits:
Adult
/
Aged
/
Aged, 80 and over
/
Humans
Language:
English
Journal:
Chinese Medical Journal
Year:
2004
Document type:
Article