Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembran e protein with folate hydrolase and NAALAdase activity. PSMA is highly expr essed in prostate cancer and the vasculature of most solid tumors, and is c urrently the target of a number of diagnostic and therapeutic strategies. P SMA is also expressed in the brain, and is involved in conversion of the ma jor neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glu tamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's d isease and schizophrenia. To facilitate analysis of the role of PSMA in car cinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 n t portion of the 5' region of the PSMA gene was able to drive the firefly l uciferase reporter gene in prostate but not breast-derived cell lines, we h ave mapped the gene encoding PSMA to 11p11-p12, however a gene homologous, but not identical, to PSMA exists on chromosome 11q14. Analysis of sequence differences between non-coding regions of the two genes suggests duplicati on and divergence occurred 32 million years ago. (C) 1998 Elsevier Science B.V. All rights reserved.