Prostate stem cell antigen: A cell surface marker overexpressed in prostate cancer

Robert E. Reiter, Zhennen Gu, Tetsuro Watabe, George Thomas, Kinga Szigeti, Elizabeth Davis, Matthew Wahl, Sazuku Nisitani, Joyce Yamashiro, Michelle M. Le Beau, Massimo Loda, Owen N. Witte

Research output: Contribution to journalArticlepeer-review

546 Scopus citations

Abstract

The identification of cell surface antigens is critical to the development of new diagnostic and therapeutic modalities for the management of prostate cancer. Prostate stem cell antigen (PSCA) is a prostate-specific gene with 30% homology to stem cell antigen 2, a member of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA encodes a 123-aa protein with an amino-terminal signal sequence, a carboxyl-terminal GPI-anchoring sequence, and multiple N-glycosylation sites. PSCA mRNA expression is prostate-specific in normal male tissues and is highly up-regulated in both androgen-dependent and -independent prostate cancer xenografts. In situ mRNA analysis localizes PSCA expression in normal prostate to the basal cell epithelium, the putative stem cell compartment of the prostate. There is moderate to strong PSCA expression in 111 of 126 (88%) prostate cancer specimens examined by in situ analysis, including high-grade prostatic intraepithelial neoplasia and androgen-dependent and androgen- independent tumors. Flow cytometric analysis demonstrates that PSCA is expressed predominantly on the cell surface and is anchored by a GPI linkage. Fluorescent in situ hybridization analysis localizes the PSCA gene to chromosome 8q24.2, a region of allelic gain in more than 80% of prostate cancers. A mouse homologue with 70% amino acid identity and similar genomic organization to human PSCA has also been identified. These results support PSCA as a target for prostate cancer diagnosis and therapy.

Original languageEnglish (US)
Pages (from-to)1735-1740
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
StatePublished - Feb 17 1998
Externally publishedYes

ASJC Scopus subject areas

  • General

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