PSCA (gene) explained

Prostate stem cell antigen is a protein that in humans is encoded by the PSCA gene.^{[1] [2]}

This gene encodes a glycosylphosphatidylinositol-anchored cell membrane glycoprotein. In addition to being highly expressed in the prostate it is also expressed in the bladder, placenta, colon, kidney, and stomach. This gene has a nonsynonymous nucleotide polymorphism at its start codon.^[2]

Clinical significance

This gene is up-regulated in a large proportion of prostate cancers and is also detected in cancers of the bladder and pancreas.^[2]

Mechanism

A study reviewing the potential role of PSCA proposed that expression of the gene is regulated through the androgen receptor complex.^[3] The proteins translated from the gene, is then glycosylated in the ER, and transported to the cell membrane where it is connected to a lipid. This results in the formation of a GPI-anchored proteins, these proteins can be often secreted by cells or play a role in cell signaling. While, the ligand activating PSCA or the downstream physiological role has not yet been determined, because of its mechanism and over expression in prostate cancer cells, PSCA can potentially serve as a biomarker for detecting cancer.^[4]

Further reading

• Gu Z, Thomas G, Yamashiro J, Shintaku IP, Dorey F, Raitano A, Witte ON, Said JW, Loda M, Reiter RE . 6 . Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer . Oncogene . 19 . 10 . 1288–96 . March 2000 . 10713670 . 10.1038/sj.onc.1203426 . free .
• Bahrenberg G, Brauers A, Joost HG, Jakse G . Reduced expression of PSCA, a member of the LY-6 family of cell surface antigens, in bladder, esophagus, and stomach tumors . Biochemical and Biophysical Research Communications . 275 . 3 . 783–8 . September 2000 . 10973799 . 10.1006/bbrc.2000.3393 .
• Amara N, Palapattu GS, Schrage M, Gu Z, Thomas GV, Dorey F, Said J, Reiter RE . 6 . Prostate stem cell antigen is overexpressed in human transitional cell carcinoma . Cancer Research . 61 . 12 . 4660–5 . June 2001 . 11406532 .
• Watabe T, Lin M, Ide H, Donjacour AA, Cunha GR, Witte ON, Reiter RE . Growth, regeneration, and tumorigenesis of the prostate activates the PSCA promoter . Proceedings of the National Academy of Sciences of the United States of America . 99 . 1 . 401–6 . January 2002 . 11752398 . 117572 . 10.1073/pnas.012574899 . 2002PNAS...99..401W . free .
• 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 . 6 . Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate . Cancer Research . 62 . 9 . 2546–53 . May 2002 . 11980648 .
• Jain A, Lam A, Vivanco I, Carey MF, Reiter RE . Identification of an androgen-dependent enhancer within the prostate stem cell antigen gene . Molecular Endocrinology . 16 . 10 . 2323–37 . October 2002 . 12351697 . 10.1210/me.2002-0004 . free .
• Tran CP, Lin C, Yamashiro J, Reiter RE . Prostate stem cell antigen is a marker of late intermediate prostate epithelial cells . Molecular Cancer Research . 1 . 2 . 113–21 . December 2002 . 12496358 .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . 6 . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Research . 13 . 10 . 2265–70 . October 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .
• Zhang Z, Henzel WJ . Signal peptide prediction based on analysis of experimentally verified cleavage sites . Protein Science . 13 . 10 . 2819–24 . October 2004 . 15340161 . 2286551 . 10.1110/ps.04682504 .
• Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Pérez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Imhof A, Caldas C, Jenuwein T, Esteller M . 6 . Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer . Nature Genetics . 37 . 4 . 391–400 . April 2005 . 15765097 . 10.1038/ng1531 . 27245550 .
• Lam JS, Yamashiro J, Shintaku IP, Vessella RL, Jenkins RB, Horvath S, Said JW, Reiter RE . 6 . Prostate stem cell antigen is overexpressed in prostate cancer metastases . Clinical Cancer Research . 11 . 7 . 2591–6 . April 2005 . 15814638 . 10.1158/1078-0432.CCR-04-1842 . free .
• Zhigang Z, Wenlu S . Complete androgen ablation suppresses prostate stem cell antigen (PSCA) mRNA expression in human prostate carcinoma . The Prostate . 65 . 4 . 299–305 . December 2005 . 16015594 . 10.1002/pros.20290 . 1951165 .
• Wente MN, Jain A, Kono E, Berberat PO, Giese T, Reber HA, Friess H, Büchler MW, Reiter RE, Hines OJ . 6 . Prostate stem cell antigen is a putative target for immunotherapy in pancreatic cancer . Pancreas . 31 . 2 . 119–25 . August 2005 . 16024997 . 10.1097/01.mpa.0000173459.81193.4d . 25132037 .
• Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS . 6 . Transcriptome analysis of human gastric cancer . Mammalian Genome . 16 . 12 . 942–54 . December 2005 . 16341674 . 10.1007/s00335-005-0075-2 . 69278 .
• Grubbs EG, Abdel-Wahab Z, Tyler DS, Pruitt SK . Utilizing quantitative polymerase chain reaction to evaluate prostate stem cell antigen as a tumor marker in pancreatic cancer . Annals of Surgical Oncology . 13 . 12 . 1645–54 . December 2006 . 16957968 . 10.1245/s10434-006-9029-5 . 8003703 .
• Morgenroth A, Cartellieri M, Schmitz M, Günes S, Weigle B, Bachmann M, Abken H, Rieber EP, Temme A . 6 . Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells . The Prostate . 67 . 10 . 1121–31 . July 2007 . 17492652 . 10.1002/pros.20608 . 30518541 .

Notes and References

1. 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 . 6 . Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer . Proceedings of the National Academy of Sciences of the United States of America . 95 . 4 . 1735–40 . February 1998 . 9465086 . 19171 . 10.1073/pnas.95.4.1735 . 1998PNAS...95.1735R . free .
2. Web site: Entrez Gene: PSCA prostate stem cell antigen.
3. Saeki N, Gu J, Yoshida T, Wu X . Prostate stem cell antigen: a Jekyll and Hyde molecule? . Clinical Cancer Research . 16 . 14 . 3533–8 . July 2010 . 20501618 . 2905486 . 10.1158/1078-0432.CCR-09-3169 .
4. Kong HK, Park JH . Characterization and function of human Ly-6/uPAR molecules . BMB Reports . 45 . 11 . 595–603 . November 2012 . 23186997 . 4133805 . 10.5483/bmbrep.2012.45.11.210 .