ISPO

Published in Cancer Detection and Prevention 2004; 28(2):88-093.

Up-regulation of hypoxia-inducible factor 1 is an early event in prostate carcinogenesis

Hua Zhong, MD, PhDa, Gregg L. Semenza, MD, PhDb, Jonathan W. Simons, MDa, Angelo M. De Marzo, MD, PhDc

aDepartment of Hematology and Oncology, Winship Cancer Institute, Emory University, 1365-B Clifton Road, N.E. Room B4328, Atlanta, GA 30322, USA bInstitute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA cDepartment of Pathology, Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding glucose transporters, glycolytic enzymes, and vascular endothelial growth factor (VEGF). HIF-1 is a major subunit of HIF-1 heterodimer. In this study, an immunohistochemical analysis of HIF-1 was focused on clinical specimens containing high-grade prostate intraepithelial neoplasia lesions since high-grade prostate intraepithelial neoplasia is considered as precursor of a majority invasive prostate adenocarcinoma and presents the increased activity of angiogenesis. HIF-1 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-1 in adjacent prostate cancer lesions was more enhanced than that in high-grade prostate intraepithelial neoplasia. The results suggest that up-regulation of HIF-1 is an early event in prostate carcinogenesis, and that HIF-1 is a potential target for prostate cancer prevention and a surrogate biomarker for monitoring pre-malignant lesions of prostate.

KEY WORDS: Prostate, High-grade prostatic intraepithelial neoplasia, Immunohistochemistry.

http://www.cancerprev.org/Journal/Issues/28/2/4865