PSCA (Prostate stem cell antigen)

2009-01-01   Adam B Raff , Andrew Gray , W Martin Kast 

Departments of Molecular Microbiology, Immunology, Obstetrics, Gynecology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA





The PSCA gene was originally identified by Reiter el al. (1998) through an analysis of genes up-regulated in the human prostate cancer LAPC-4 xenograft model. The PSCA gene is located on chromosome 8q24.2.


In normal human tissues, PSCA mRNA expression is found in the prostate, with lower expression in placenta and very low expression in kidney and small intestine (Reiter et al., 1998; Cunha et al., 2006). Within normal human prostate sections, in situ hybridizations by Reiter el al. (1998) demonstrated PSCA mRNA expression in the subjacent basal cells, while Ross et al. (2002) demonstrated PSCA mRNA expression in the secretory luminal cells. These contrasting results may be due to sampling error from relatively small biopsies, since PSCA protein expression was seen in both cell types (see below).



The PSCA gene encodes a 123 amino acid cell surface protein with a molecular weight of 10-24 kDa (Reiter et al., 1998). Inaccurately named for its 30% homology to stem cell antigen type 2 (SCA-2), an immature lymphocyte cell surface marker, PSCA is neither a marker for a stem cell population nor is it exclusively expressed in the prostate. Like SCA-2 however, PSCA is a member of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI) anchored surface proteins.


In the human prostate, PSCA protein expression is found in both the basal and secretory epithelial cell layers, along with the neuroendocrine cells. Additionally, PSCA protein expression was demonstrated in the placenta, the bladder, the neuroendocrine cells of the stomach and colon, and weakly in the kidneys excluding the glomeruli (Gu et al., 2000).


PSCA is localized to the cell surface, anchored by a GPI linkage.


Although the function of PSCA is currently unknown, PSCA homologues give some insight into possible functions. It has been previously shown that proteins in the Thy-1 family have been reported to function in T cell activation (Presky et al., 1990) and proliferation, stem cell survival, and cytokine and growth factor response (Rege et al., 2006), while the family of Ly-6 genes has been associated with carcinogenesis (Treister et al., 1998; Witz et al., 2000), cellular activation (Malek et al., 1986) and cell adhesion of tumor cells (Eshel et al., 2000). PSCA does not seem to be critical for normal development or urogenital function since a PSCA knockout mouse created by Moore et al. (2008) was viable, grew to adulthood and had normal litters. Additionally, these PSCA knockout mice did not have an increased incidence of carcinogenesis.


A murine PSCA (mPSCA) homologue was also identified by Reiter et al. (1998) and it is located on chromosome 15. mPSCA has 70% homology to human PSCA at the nucleotide and amino acid levels.



While no mutation is known for PSCA, a recent study by the Study Group of Millennium Genome Project for Cancer (2008) found a significant association between two Single Nucleotide Polymorphisms (SNPs) in the PSCA gene and diffuse-type gastric cancer.

Implicated in

Entity name
Prostate Cancer
In human prostate cancer, PSCA over-expression is present in primary human prostate tumors and residual tumors removed after androgen ablation therapy (Reiter et al., 1998; Gu et al., 2000). There is a significant correlation between PSCA expression and seminal vesicle invasion, capsular involvement (Han et al., 2004), Gleason score, tumor stage and progression to androgen-independence (Gu et al., 2000). PSCA expression also correlates with metastasis, with a higher percentage of metastatic tumors expressing PSCA compared to non-metastatic tumors (Ross et al., 2002). In particular, bone marrow metastases show relatively higher intensity of PSCA expression compared to lymph node and liver metastases (Gu et al., 2000; Lam et al., 2005).
PSCA has been tested as a prostate cancer biomarker, with limited but interesting results. One study by Hara et al. (2002) screened for the presence of PSCA mRNA in a milliliter of patient blood via reverse transcription-polymerase chain reaction (RT-PCR) but found only 13.8% of prostate cancer cases positive for PSCA mRNA. However, this study also found that stage IV, PSCA mRNA positive patients correlated with a lower disease-free survival compared to stage IV, PSCA mRNA negative patients. In a separate study by Zhigang et al. (2008), 23.7% of men with benign prostatic hyperplasia (BPH) treated with transurethral resection of the prostate (TURP) who were positive for PSCA mRNA expression went on to develop prostate cancer versus only 1.0% of patients who were negative.
PSCAs role in prostate carcinogenesis remains unknown. The location of the PSCA gene at 8q24.2 has some interesting correlations however. Chromosome 8q is commonly amplified in metastatic and recurrent prostate carcinoma, and this amplification is associated with a poor prognosis (Visakorpi et al., 1995; Sato et al., 1999). Additionally, PSCA expression may be a marker for MYC amplification, a common mutation in prostate cancer, since both genes are located close to one another (Qian et al., 1995; Jenkins et al., 1997; Jalkut et al., 2002).
Entity name
Additional cancers
In addition to the identification of PSCA as a prostate tumor associated protein, several other tumors have shown associations with PSCA expression including pancreatic adenocarcinoma (Argani et al., 2001; Iacobuzio-Donahue et al., 2002; Wente et al., 2005), transitional cell carcinoma (Amara et al., 2001; Elsamman et al., 2006), renal cell carcinoma (Elsamman et al., 2006) and diffuse-type gastric cancer (The Study Group of Millennium Genome Project for Cancer, 2008).


Pubmed IDLast YearTitleAuthors
114065322001Prostate stem cell antigen is overexpressed in human transitional cell carcinoma.Amara N et al
113890522001Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma.Argani P et al
160460562006Tissue-specificity of prostate specific antigens: comparative analysis of transcript levels in prostate and non-prostatic tissues.Cunha AC et al
166867112006Prostate stem cell antigen predicts tumour recurrence in superficial transitional cell carcinoma of the urinary bladder.Elsamman E et al
169257702006The expression of prostate stem cell antigen in human clear cell renal cell carcinoma: a quantitative reverse transcriptase-polymerase chain reaction analysis.Elsamman EM et al
107775812000The GPI-linked Ly-6 antigen E48 regulates expression levels of the FX enzyme and of E-selectin ligands on head and neck squamous carcinoma cells.Eshel R et al
182454882008Prostate stem cell antigen vaccination induces a long-term protective immune response against prostate cancer in the absence of autoimmunity.Garcia-Hernandez Mde L et al
107136702000Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.Gu Z et al
119437092002Discovery of novel tumor markers of pancreatic cancer using global gene expression technology.Iacobuzio-Donahue CA et al
121724272002Role of prostate stem cell antigen in prostate cancer research.Jalkut MW et al
90124851997Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization.Jenkins RB et al
158146382005Prostate stem cell antigen is overexpressed in prostate cancer metastases.Lam JS et al
34890601986Role of Ly-6 in lymphocyte activation. II. Induction of T cell activation by monoclonal anti-Ly-6 antibodies.Malek TR et al
180447302008Deletion of PSCA increases metastasis of TRAMP-induced prostate tumors without altering primary tumor formation.Moore ML et al
19672761990Role of phosphatidylinositol-anchored proteins in T cell activation.Presky DH et al
75856101995Chromosomal anomalies in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization.Qian J et al
188382142009Prostate stem cell antigen: a prospective therapeutic and diagnostic target.Raff AB et al
169961532006Thy-1, a versatile modulator of signaling affecting cellular adhesion, proliferation, survival, and cytokine/growth factor responses.Rege TA et al
94650861998Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer.Reiter RE et al
119806482002Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate.Ross S et al
104914351999Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma.Sato K et al
184880302008Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer.Sakamoto H et al
96505691998Expression of Ly-6, a marker for highly malignant murine tumor cells, is regulated by growth conditions and stress.Treister A et al
75291341995Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization.Visakorpi T et al
160249972005Prostate stem cell antigen is a putative target for immunotherapy in pancreatic cancer.Wente MN et al
107620162000Differential expression of genes by tumor cells of a low or a high malignancy phenotype: the case of murine and human Ly-6 proteins.Witz IP et al

Other Information

Locus ID:

NCBI: 8000
MIM: 602470
HGNC: 9500
Ensembl: ENSG00000167653


dbSNP: 8000
ClinVar: 8000
TCGA: ENSG00000167653


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
Post-translational modification: synthesis of GPI-anchored proteinsREACTOMER-HSA-163125

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
184880302008Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer.127
184880302008Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer.127
196489202009Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.107
196489202009Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.107
205016182010Prostate stem cell antigen: a Jekyll and Hyde molecule?59
223879982012A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population.49
124963582002Prostate stem cell antigen is a marker of late intermediate prostate epithelial cells.42
224161222012Common genetic variants in the PSCA gene influence gene expression and bladder cancer risk.42
193437342009Expression of the gastrin-releasing peptide receptor, the prostate stem cell antigen and the prostate-specific membrane antigen in lymph node and bone metastases of prostate cancer.38
210707792011A functional single nucleotide polymorphism in mucin 1, at chromosome 1q22, determines susceptibility to diffuse-type gastric cancer.37


Adam B Raff ; Andrew Gray ; W Martin Kast

PSCA (Prostate stem cell antigen)

Atlas Genet Cytogenet Oncol Haematol. 2009-01-01

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