Expression analysis of δ‐catenin and prostate‐specific membrane antigen: Their potential as diagnostic markers for prostate cancer

The current approach to prostate cancer diagnosis has major limitations including the inability of prostate‐specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3‐fold greater in 6 tumour tissues than in 1 nontumour sample and 1 BPH sample. Real‐time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and 11 BPH samples. Two genes, δ‐catenin (delta‐catenin; CTNND2) and prostate‐specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for δ‐catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified δ‐catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer. © 2002 Wiley‐Liss, Inc.

[1]  T. Stamey,et al.  Zonal Distribution of Prostatic Adenocarcinoma: Correlation with Histologic Pattern and Direction of Spread , 1988, The American journal of surgical pathology.

[2]  L. Tsai,et al.  A family of human cdc2‐related protein kinases. , 1992, The EMBO journal.

[3]  E. Sprinzak,et al.  Prediction of gene function by genome-scale expression analysis: prostate cancer-associated genes. , 1999, Genome research.

[4]  P. Schellhammer,et al.  Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. , 1995, Urologic oncology.

[5]  J. Schalken,et al.  Complex cadherin expression in human prostate cancer cells , 2000, International journal of cancer.

[6]  J. Fletcher,et al.  Expression of metallopanstimulin and oncogenesis in human prostatic carcinoma. , 1997, Anticancer research.

[7]  A. Ullrich,et al.  Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. , 1995, Oncogene.

[8]  M. Oberholzer,et al.  Light microscopic stereological analysis of the normal human prostate and of benign prostatic hyperplasia. , 1979, The Journal of urology.

[9]  P. Pandolfi,et al.  Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse , 2001, Nature Genetics.

[10]  M. Rubin,et al.  Tissue microarray assessment of prostate cancer tumor proliferation in African- American and white men. , 2000, Journal of the National Cancer Institute.

[11]  J. Schalken,et al.  Cadherin switching in human prostate cancer progression. , 2000, Cancer research.

[12]  Daniel S. Miller,et al.  Annual report to the nation on the status of cancer, 1973-1996, with a special section on lung cancer and tobacco smoking. , 1999, Journal of the National Cancer Institute.

[13]  M. Bittner,et al.  Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. , 2001, Cancer research.

[14]  E. Maestrini,et al.  A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Rimm,et al.  The expression of p120ctn protein in breast cancer is independent of alpha- and beta-catenin and E-cadherin. , 1998, The American journal of pathology.

[16]  J. Nakayama,et al.  Enhanced expression of prostate-specific membrane antigen gene in prostate cancer as revealed by in situ hybridization. , 1997, Cancer research.

[17]  L. Martínez-Piñeiro,et al.  Determination of the Percentage of Free Prostate–Specific Antigen Helps to Avoid Unnecessary Biopsies in Men with Normal Rectal Examinations and Total Prostate–Specific Antigen of 4–10 ng/ml , 2000, European Urology.

[18]  C C Schulman,et al.  Optimal predictors of prostate cancer on repeat prostate biopsy: a prospective study of 1,051 men. , 2000, The Journal of urology.

[19]  K. Kosik,et al.  δ-catenin, an Adhesive Junction–associated Protein Which Promotes Cell Scattering , 1999, The Journal of cell biology.

[20]  W. Fair,et al.  Alternatively spliced variants of prostate-specific membrane antigen RNA: ratio of expression as a potential measurement of progression. , 1995, Cancer research.

[21]  M. Loda,et al.  Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Thomas D. Schmittgen,et al.  Effect of experimental treatment on housekeeping gene expression: validation by real-time, quantitative RT-PCR. , 2000, Journal of biochemical and biophysical methods.

[23]  J. Schalken,et al.  Decreased expression of alpha-catenin is associated with poor prognosis of patients with localized renal cell carcinoma. , 1998, International Journal of Cancer.

[24]  M. Lovett,et al.  Presenilin 1 interaction in the brain with a novel member of the Armadillo family , 1997, Neuroreport.

[25]  T. Ried,et al.  Cell cycle-dependent expression of Nek2, a novel human protein kinase related to the NIMA mitotic regulator of Aspergillus nidulans. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[26]  J. Schalken,et al.  Decreased expression of α‐catenin is associated with poor prognosis of patients with localized renal cell carcinoma , 1997 .

[27]  L. Liotta,et al.  Identification of a novel transcript up-regulated in a clinically aggressive prostate carcinoma. , 1997, Urology.

[28]  T. Nevalainen,et al.  Group II phospholipase A2 in human male reproductive organs and genital tumors , 1998, The Prostate.

[29]  R. Hubert,et al.  STEAP: a prostate-specific cell-surface antigen highly expressed in human prostate tumors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  W Pruzanski,et al.  Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid. , 1989, The Journal of biological chemistry.

[31]  W. Isaacs,et al.  DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. , 1999, Cancer research.

[32]  Roger E Bumgarner,et al.  Prostate short-chain dehydrogenase reductase 1 (PSDR1): a new member of the short-chain steroid dehydrogenase/reductase family highly expressed in normal and neoplastic prostate epithelium. , 2001, Cancer research.

[33]  V. Reuter,et al.  Prostate-specific membrane antigen is produced in tumor-associated neovasculature. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[34]  W. Fair,et al.  Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. , 1993, Cancer research.

[35]  A W Partin,et al.  Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. , 1997, JAMA.

[36]  W. Franke,et al.  Identification and localization of a neurally expressed member of the plakoglobin/armadillo multigene family. , 1997, Differentiation; research in biological diversity.

[37]  J. Clements,et al.  Kallikrein gene family expression in the rat ovary: localization to the granulosa cell. , 1995, Endocrinology.

[38]  P. Weijerman,et al.  Lipofection-mediated immortalization of human prostatic epithelial cells of normal and malignant origin using human papillomavirus type 18 DNA. , 1994, Cancer research.

[39]  M. Plebani,et al.  Total PSA, free PSA/total PSA ratio, and molecular PSA detection in prostate cancer: which is clinically effective and when? , 2000, Urology.

[40]  V. Reuter,et al.  Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. , 1999, Cancer research.

[41]  Siavash Ghaffari,et al.  A candidate prostate cancer susceptibility gene at chromosome 17p , 2001, Nature Genetics.

[42]  M. Loda,et al.  Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer , 2000, Oncogene.

[43]  J. Welsh,et al.  Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. , 2001, Cancer research.

[44]  P. Schellhammer,et al.  Determination of the "reflex range" and appropriate cutpoints for percent free prostate-specific antigen in 413 men referred for prostatic evaluation using the AxSYM system. , 1997, Urology.

[45]  S. Dhanasekaran,et al.  Delineation of prognostic biomarkers in prostate cancer , 2001, Nature.

[46]  V. Sukhatme,et al.  cDNA sequence of the human cellular early growth response gene Egr-1. , 1990, Nucleic acids research.

[47]  J. Isaacs,et al.  Prostate‐specific membrane antigen (PSMA) enzyme activity is elevated in prostate cancer cells , 2000, The Prostate.

[48]  P. Kantoff,et al.  Two differentially expressed genes in normal human prostate tissue and in carcinoma. , 1996, Cancer research.

[49]  T. P. Ball,et al.  The lack of predictive value of prostate specific antigen density in the detection of prostate cancer in patients with normal rectal examinations and intermediate prostate specific antigen levels. , 1995, The Journal of urology.

[50]  N. Konishi,et al.  E-cadherin and α-, β- and γ-catenin expression in prostate cancers: correlation with tumour invasion , 1999, British Journal of Cancer.

[51]  T C Gasser,et al.  Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. , 1999, Cancer research.