title: Hypoxia-inducible factor 1 alpha (HIF-1 alpha) gene expression in human ovarian carcinoma.
abstract: Hypoxia-inducible factor 1 alpha (HIF-1 alpha) that regulates genes involved in response to hypoxia and promotes neo-angiogenesis, is a transcriptional factor for vascular endothelial cell growth factor (VEGF). The aim of this study was to examine the expression of HIF-1 alpha and VEGF gene expressions and their relation to angiogenesis, clinicopathologic variables and survival in the patient with human ovarian carcinoma. We retrospectively analyzed HIF-1 alpha and VEGF gene expression levels using reverse transcriptase polymerase chain reaction (RT-PCR) in 60 ovarian carcinomas. Intratumoral microvessel density (IMD) was assessed by immunostaining endothelial cells, using anti-CD 31 antibody in frozen sections. The relationships between the expression level of these genes, IMD and clinicopathologic variables were evaluated by Student's t-test and chi-square tests. Survival analysis was performed by Kaplan-Meier curves. HIF-1 alpha or VEGF gene expression level was independent of age, clinical stage and histological subtype besides grade of tumor. There was no relationship between HIF-1 alpha or VEGF gene expression level and IMD in all carcinomas (R=0.118 and 0.224, respectively). In addition, a weak association between HIF-1 alpha and VEGF gene expression level was observed (R=0.300, P=0.020). The association between VEGF gene expression and IMD was observed (R=0.501, P=0.016). However, no association between IMD and HIF-1 alpha gene expression was observed. Further, both HIF-1 alpha and VEGF gene expression levels had no effect on survival in the patient with ovarian carcinoma. These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of some type of ovarian carcinoma, but the expression levels of both genes have no effect on survival in the patients with ovarian carcinoma.
authors.affiliation: Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8570, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kanzaki
authors.forename: Kohkichi
authors.initials: K
authors.lastname: Hata
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Katabuchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takebayashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000096:biosynthesis; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008222:Lymphokines / Q000096:biosynthesis; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D018952:Antigens, CD34; D016228:Endothelial Growth Factors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors