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PSCA (Prostate stem cell antigen)

Written2009-01Adam 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

(Note : for Links provided by Atlas : click)


Alias (NCBI)PRO232
LocusID (NCBI) 8000
Atlas_Id 41881
Location 8q24.3  [Link to chromosome band 8q24]
Location_base_pair Starts at 142680495 and ends at 142682725 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PSCA.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
PSCA (8q24.3)::AVL9 (7p14.3)


Description 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.
Transcription 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).


Description 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.
Expression 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).
Localisation PSCA is localized to the cell surface, anchored by a GPI linkage.
Function 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.
Homology 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.


Note 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 Prostate Cancer
Note 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).
Prognosis 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.
Oncogenesis PSCA's 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 Additional cancers
Note 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).

To be noted

The current role of PSCA as a diagnostic, prognostic and therapeutic tool was recently reviewed by our laboratory (Raff et al., 2008). While the use of PSCA as a target in the treatment of human prostate cancer is not covered here, it represents an ideal choice for immunotherapy due to its overexpression in prostate tumors and limited expression in normal tissues. For example, our laboratory recently demonstrated that PSCA vaccination of TRAMP mice that spontaneously generate prostate cancer conferred a 90% survival rate at 12 months of age in contrast to control mice which had all succumbed to prostate cancer or had heavy tumor loads (Garcia-Hernandez et al., 2008).


Prostate stem cell antigen is overexpressed in human transitional cell carcinoma.
Amara N, Palapattu GS, Schrage M, Gu Z, Thomas GV, Dorey F, Said J, Reiter RE.
Cancer Res. 2001 Jun 15;61(12):4660-5.
PMID 11406532
Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma.
Argani P, Rosty C, Reiter RE, Wilentz RE, Murugesan SR, Leach SD, Ryu B, Skinner HG, Goggins M, Jaffee EM, Yeo CJ, Cameron JL, Kern SE, Hruban RH.
Cancer Res. 2001 Jun 1;61(11):4320-4.
PMID 11389052
Tissue-specificity of prostate specific antigens: comparative analysis of transcript levels in prostate and non-prostatic tissues.
Cunha AC, Weigle B, Kiessling A, Bachmann M, Rieber EP.
Cancer Lett. 2006 May 18;236(2):229-38. Epub 2005 Jul 19.
PMID 16046056
Prostate stem cell antigen predicts tumour recurrence in superficial transitional cell carcinoma of the urinary bladder.
Elsamman E, Fukumori T, Kasai T, Nakatsuji H, Nishitani MA, Toida K, Ali N, Kanayama HO.
BJU Int. 2006 Jun;97(6):1202-7.
PMID 16686711
The expression of prostate stem cell antigen in human clear cell renal cell carcinoma: a quantitative reverse transcriptase-polymerase chain reaction analysis.
Elsamman EM, Fukumori T, Tanimoto S, Nakanishi R, Takahashi M, Toida K, Kanayama HO.
BJU Int. 2006 Sep;98(3):668-73.
PMID 16925770
The 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, Zanin A, Sagi-Assif O, Meshel T, Smorodinsky NI, Dwir O, Alon R, Brakenhoff R, van Dongen G, Witz IP.
J Biol Chem. 2000 Apr 28;275(17):12833-40.
PMID 10777581
Prostate stem cell antigen vaccination induces a long-term protective immune response against prostate cancer in the absence of autoimmunity.
Garcia-Hernandez Mde L, Gray A, Hubby B, Klinger OJ, Kast WM.
Cancer Res. 2008 Feb 1;68(3):861-9.
PMID 18245488
Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.
Gu Z, Thomas G, Yamashiro J, Shintaku IP, Dorey F, Raitano A, Witte ON, Said JW, Loda M, Reiter RE.
Oncogene. 2000 Mar 2;19(10):1288-96.
PMID 10713670
Discovery of novel tumor markers of pancreatic cancer using global gene expression technology.
Iacobuzio-Donahue CA, Maitra A, Shen-Ong GL, van Heek T, Ashfaq R, Meyer R, Walter K, Berg K, Hollingsworth MA, Cameron JL, Yeo CJ, Kern SE, Goggins M, Hruban RH.
Am J Pathol. 2002 Apr;160(4):1239-49.
PMID 11943709
Role of prostate stem cell antigen in prostate cancer research.
Jalkut MW, Reiter RE.
Curr Opin Urol. 2002 Sep;12(5):401-6. (REVIEW)
PMID 12172427
Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization.
Jenkins RB, Qian J, Lieber MM, Bostwick DG.
Cancer Res. 1997 Feb 1;57(3):524-31.
PMID 9012485
Prostate stem cell antigen is overexpressed in prostate cancer metastases.
Lam JS, Yamashiro J, Shintaku IP, Vessella RL, Jenkins RB, Horvath S, Said JW, Reiter RE.
Clin Cancer Res. 2005 Apr 1;11(7):2591-6.
PMID 15814638
Role of Ly-6 in lymphocyte activation. II. Induction of T cell activation by monoclonal anti-Ly-6 antibodies.
Malek TR, Ortega G, Chan C, Kroczek RA, Shevach EM.
J Exp Med. 1986 Sep 1;164(3):709-22.
PMID 3489060
Deletion of PSCA increases metastasis of TRAMP-induced prostate tumors without altering primary tumor formation.
Moore ML, Teitell MA, Kim Y, Watabe T, Reiter RE, Witte ON, Dubey P.
Prostate. 2008 Feb 1;68(2):139-51.
PMID 18044730
Role of phosphatidylinositol-anchored proteins in T cell activation.
Presky DH, Low MG, Shevach EM.
J Immunol. 1990 Feb 1;144(3):860-8.
PMID 1967276
Chromosomal anomalies in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization.
Qian J, Bostwick DG, Takahashi S, Borell TJ, Herath JF, Lieber MM, Jenkins RB.
Cancer Res. 1995 Nov 15;55(22):5408-14.
PMID 7585610
Prostate stem cell antigen: A prospective therapeutic and diagnostic target.
Raff AB, Gray A, Kast WM.
Cancer Lett. 2008 Oct 4. [Epub ahead of print] (REVIEW)
PMID 18838214
Thy-1, a versatile modulator of signaling affecting cellular adhesion, proliferation, survival, and cytokine/growth factor responses.
Rege TA, Hagood JS.
Biochim Biophys Acta. 2006 Oct;1763(10):991-9. Epub 2006 Aug 18.
PMID 16996153
Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer.
Reiter RE, Gu Z, Watabe T, Thomas G, Szigeti K, Davis E, Wahl M, Nisitani S, Yamashiro J, Le Beau MM, Loda M, Witte ON.
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1735-40.
PMID 9465086
Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate.
Ross S, Spencer SD, Holcomb I, Tan C, Hongo J, Devaux B, Rangell L, Keller GA, Schow P, Steeves RM, Lutz RJ, Frantz G, Hillan K, Peale F, Tobin P, Eberhard D, Rubin MA, Lasky LA, Koeppen H.
Cancer Res. 2002 May 1;62(9):2546-53.
PMID 11980648
Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma.
Sato K, Qian J, Slezak JM, Lieber MM, Bostwick DG, Bergstralh EJ, Jenkins RB.
J Natl Cancer Inst. 1999 Sep 15;91(18):1574-80.
PMID 10491435
Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer.
Study Group of Millennium Genome Project for Cancer, Sakamoto H, Yoshimura K, Saeki N, Katai H, Shimoda T, Matsuno Y, Saito D, Sugimura H, Tanioka F, Kato S, Matsukura N, Matsuda N, Nakamura T, Hyodo I, Nishina T, Yasui W, Hirose H, Hayashi M, Toshiro E, Ohnami S, Sekine A, Sato Y, Totsuka H, Ando M, Takemura R, Takahashi Y, Ohdaira M, Aoki K, Honmyo I, Chiku S, Aoyagi K, Sasaki H, Ohnami S, Yanagihara K, Yoon KA, Kook MC, Lee YS, Park SR, Kim CG, Choi IJ, Yoshida T, Nakamura Y, Hirohashi S.
Nat Genet. 2008 Jun;40(6):730-40. Epub 2008 May 18.
PMID 18488030
Expression of Ly-6, a marker for highly malignant murine tumor cells, is regulated by growth conditions and stress.
Treister A, Sagi-Assif O, Meer M, Smorodinsky NI, Anavi R, Golan I, Meshel T, Kahana O, Eshel R, Katz BZ, Shevach E, Witz IP.
Int J Cancer. 1998 Jul 17;77(2):306-13.
PMID 9650569
Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization.
Visakorpi T, Kallioniemi AH, Syvanen AC, Hyytinen ER, Karhu R, Tammela T, Isola JJ, Kallioniemi OP.
Cancer Res. 1995 Jan 15;55(2):342-7.
PMID 7529134
Prostate stem cell antigen is a putative target for immunotherapy in pancreatic cancer.
Wente MN, Jain A, Kono E, Berberat PO, Giese T, Reber HA, Friess H, Buchler MW, Reiter RE, Hines OJ.
Pancreas. 2005 Aug;31(2):119-25.
PMID 16024997
Differential 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.
J Cell Biochem Suppl. 2000;34:61-6. (REVIEW)
PMID 10762016


This paper should be referenced as such :
Raff, AB ; Gray, A ; Kast, WM
PSCA (Prostate stem cell antigen)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(12):960-962.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)PSCA   9500
Entrez_Gene (NCBI)PSCA    prostate stem cell antigen
GeneCards (Weizmann)PSCA
Ensembl hg19 (Hinxton)ENSG00000167653 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000167653 [Gene_View]  ENSG00000167653 [Sequence]  chr8:142680495-142682725 [Contig_View]  PSCA [Vega]
ICGC DataPortalENSG00000167653
Genatlas (Paris)PSCA
SOURCE (Princeton)PSCA
Genetics Home Reference (NIH)PSCA
Genomic and cartography
GoldenPath hg38 (UCSC)PSCA  -     chr8:142680495-142682725 +  8q24.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PSCA  -     8q24.3   [Description]    (hg19-Feb_2009)
GoldenPathPSCA - 8q24.3 [CytoView hg19]  PSCA - 8q24.3 [CytoView hg38]
Genome Data Viewer NCBIPSCA [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF043498 AI685668 AJ297436 AY358912 BC023582
RefSeq transcript (Entrez)NM_005672
Consensus coding sequences : CCDS (NCBI)PSCA
Gene ExpressionPSCA [ NCBI-GEO ]   PSCA [ EBI - ARRAY_EXPRESS ]   PSCA [ SEEK ]   PSCA [ MEM ]
Gene Expression Viewer (FireBrowse)PSCA [ Firebrowse - Broad ]
GenevisibleExpression of PSCA in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8000
GTEX Portal (Tissue expression)PSCA
Human Protein AtlasENSG00000167653-PSCA [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO43653   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO43653  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO43653
Domains : Interpro (EBI)LY6_UPA_recep-like   
Domain families : Pfam (Sanger)UPAR_LY6 (PF00021)   
Domain families : Pfam (NCBI)pfam00021   
Domain families : Smart (EMBL)LU (SM00134)  
Conserved Domain (NCBI)PSCA
AlphaFold pdb e-kbO43653   
Human Protein Atlas [tissue]ENSG00000167653-PSCA [tissue]
Protein Interaction databases
IntAct (EBI)O43653
Ontologies - Pathways
Ontology : AmiGOextracellular region  plasma membrane  plasma membrane  plasma membrane  anchored component of membrane  acetylcholine receptor binding  extracellular exosome  negative regulation of ERK1 and ERK2 cascade  regulation of neurotransmitter receptor activity  
Ontology : EGO-EBIextracellular region  plasma membrane  plasma membrane  plasma membrane  anchored component of membrane  acetylcholine receptor binding  extracellular exosome  negative regulation of ERK1 and ERK2 cascade  regulation of neurotransmitter receptor activity  
REACTOMEO43653 [protein]
REACTOME PathwaysR-HSA-163125 [pathway]   
NDEx NetworkPSCA
Atlas of Cancer Signalling NetworkPSCA
Wikipedia pathwaysPSCA
Orthology - Evolution
GeneTree (enSembl)ENSG00000167653
Phylogenetic Trees/Animal Genes : TreeFamPSCA
Homologs : HomoloGenePSCA
Homology/Alignments : Family Browser (UCSC)PSCA
Gene fusions - Rearrangements
Fusion : MitelmanPSCA::AVL9 [8q24.3/7p14.3]  
Fusion : QuiverPSCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPSCA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PSCA
Exome Variant ServerPSCA
GNOMAD BrowserENSG00000167653
Varsome BrowserPSCA
ACMGPSCA variants
Genomic Variants (DGV)PSCA [DGVbeta]
DECIPHERPSCA [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPSCA 
ICGC Data PortalPSCA 
TCGA Data PortalPSCA 
Broad Tumor PortalPSCA
OASIS PortalPSCA [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPSCA  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPSCA
Mutations and Diseases : HGMDPSCA
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)PSCA
DoCM (Curated mutations)PSCA
CIViC (Clinical Interpretations of Variants in Cancer)PSCA
NCG (London)PSCA
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PSCA
NextProtO43653 [Medical]
Target ValidationPSCA
Huge Navigator PSCA [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDPSCA
Pharm GKB GenePA33847
Clinical trialPSCA
DataMed IndexPSCA
PubMed136 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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