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

Denise S. O'Keefe, Sai L. Su, Dean J. Bacich, Yutaka Horiguchi, Ying Luo, C. Thomas Powell, Dorothea Zandvliet, Pamela J. Russell, Peter L. Molloy, Norma J. Nowak, Thomas B. Shows, Cami Mullins, Raymond A. Vonder Haar, William R. Fair, Warren D.W. Heston

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane protein with folate hydrolase and NAALAdase activity. PSMA is highly expressed in prostate cancer and the vasculature of most solid tumors, and is currently the target of a number of diagnostic and therapeutic strategies. PSMA is also expressed in the brain, and is involved in conversion of the major neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glutamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and schizophrenia. To facilitate analysis of the role of PSMA in carcinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 nt portion of the 5' region of the PSMA gene was able to drive the firefly luciferase reporter gene in prostate but not breast- derived cell lines. We have 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 duplication and divergence occurred 22 million years ago.

Original languageEnglish (US)
Pages (from-to)113-127
Number of pages15
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1443
Issue number1-2
DOIs
StatePublished - Nov 26 1998
Externally publishedYes

Keywords

  • Gene duplication
  • PSM
  • Promoter
  • Prostate cancer
  • Prostate-specific membrane antigen

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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