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

  • Robert E. Reiter
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Zhennen Gu
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Tetsuro Watabe
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • George Thomas
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Kinga Szigeti
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Elizabeth Davis
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Matthew Wahl
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Sazuku Nisitani
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Joyce Yamashiro
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Michelle M. Le Beau
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Massimo Loda
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215
  • Owen N. Witte
    Departments of Urology, Howard Hughes Medical Institute, and Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215

抄録

<jats:p> 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. <jats:italic>In situ</jats:italic> 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 <jats:italic>in situ</jats:italic> 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 <jats:italic>in situ</jats:italic> 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. </jats:p>

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