title: Up-regulation of hypoxia-inducible factor 1alpha is an early event in prostate carcinogenesis.
abstract: Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes encoding glucose transporters, glycolytic enzymes, and vascular endothelial growth factor (VEGF). HIF-1alpha is a major subunit of HIF-1 heterodimer. In this study, an immunohistochemical analysis of HIF-1alpha was focused on clinical specimens containing high-grade prostate intraepithelial neoplasia lesions since high-grade prostate intraepithelial neoplasia is considered the precursor of a majority of invasive prostate adenocarcinoma and presents the increased activity of angiogenesis. HIF-1alpha was up-regulated in 11 of 14 high-grade prostate intraepithelial neoplasia lesions identified in a total 10 prostate biopsies relative to the respective normal epithelium, stromal cells, and benign prostatic hyperplasia (BPH). Moreover, up-regulation of HIF-1alpha in adjacent prostate cancer lesions was more enhanced than in high-grade prostate intraepithelial neoplasia. The results suggest that up-regulation of HIF-1alpha is an early event in prostate carcinogenesis, and that HIF-1alpha may become a potential target for prostate cancer prevention and a surrogate biomarker for monitoring pre-malignant lesions of the prostate.
authors.affiliation: Department of Hematology and Oncology, Winship Cancer Institute, Emory University, 1365-B Clifton Road, N.E. Room B4328, Atlanta, GA 30322, USA. hua.zhong@emoryhealthcare.org
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Simons
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis* / Q000502:physiology; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000737:chemistry*; D014157:Transcription Factors; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors