Amplification of hypoxia-inducible factor 1 alpha gene in prostate cancer

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates the expression of genes associated with adaptation to reduced oxygen press ure. Increased expression of HIF-1 alpha gene (NIF1A) has been found in the majority of prostate carcinomas. In addition, the PC-3 prostate cancer cel l line has been shown to express the gene even under normoxic conditions. B y comparative genomic hybridization (CGH), we have earlier shown that the P C-3 cell line contains a high-level amplification in the chromosomal region harboring the HIF1A gene. Here, we first fine mapped the gene to locus 14q 23 by fluorescence in situ hybridization (FISH). The gene was then shown to be highly amplified in the PC-3 cell line. Subsequently, the copy number o f the HIF1A gene was studied in 5 other prostate cancer cell lines (LNCaP, DU-145, NCI-H660, Tsu-Pr, JCA-1) and in 117 prostate tumors representing bo th hormone-dependent and -refractory disease as well as primary and metasta tic lesions. No high-level amplifications of the HIF1A gene were found. Add itional copies of the gene were seen in all of the cell lines and in 36% of the tumors. There was no association between the tumor type and the copy n umber alterations of the gene. In conclusion, high-level amplification of t he HIF1A gene may explain the overexpression of the gene in the PC-3 prosta te cancer cell line. However, such high-level amplification seems to be ver y rare in prostate cancer. (C) 2001 Elsevier Science Inc. All rights reserv ed.