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.