The Anterior Gradient 2 (AGR2) Gene Is Overexpressed in Prostate Cancer and May Be Useful as a Urine Sediment Marker for Prostate Cancer Detection

被引:77
作者
Bu, Huajie [1 ]
Bormann, Stefanie [2 ]
Schaefer, Georg [1 ]
Horninger, Wolfgang [1 ]
Massoner, Petra [1 ]
Neeb, Antje [2 ]
Lakshmanan, Vinoth-Kumar [2 ]
Maddalo, Danilo [2 ]
Nestl, Andrea [2 ]
Sueltmann, Holger [3 ]
Cato, Andrew C. B. [2 ]
Klocker, Helmut [1 ]
机构
[1] Innsbruck Med Univ, Dept Urol, Div Expt Urol, A-6020 Innsbruck, Austria
[2] Karlsruhe Inst Technol, Inst Toxicol & Genet, Eggenstein Leopoldshafen, Germany
[3] German Canc Res Ctr, Working Grp Canc Genome Res, D-6900 Heidelberg, Germany
关键词
urine prostate cancer marker; cell migration; cell-cycle progression; invasion; metastasis; ESTROGEN-RECEPTOR; HUMAN HOMOLOG; CELL-CYCLE; EXPRESSION; PROTEIN; CARCINOMA; PROLIFERATION; PROGRESSION; SURVIVAL; STRESS;
D O I
10.1002/pros.21273
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND. AGR2 is a member of the endoplasmatic reticulum protein disulphide isomerase gene family implicated in tumor metastasis. Its expression pattern, function, and utility as a marker remains to be further investigated. METHODS. Using real-time RT-PCR and immunohistochemistry, changes of expression in different tumor stages were explored in microdissected tumor samples. AGR2 transcript level in urine sediments was scrutinized for suitability as a tumor marker. AGR2 androgen regulation and function were analyzed in cellular prostate cancer models. RESULTS. AGR2 is highly expressed in prostate cancer compared to benign tissue in particular also in low-grade tumors and PIN lesions. AGR2 transcripts were detected in urine sediments of patients undergoing prostate biopsy with significantly higher levels in tumor patients. The urine AGR2/PSA transcript ratio allowed much better discrimination between cancer and benign patients than serum total PSA or % free PSA. Prostate tumor cells express and secrete variable amounts of AGR2 protein, the highest level was found in PC3 cells. In androgen receptor-positive cell lines AGR2 is upregulated by androgens. Increased expression enhanced the migratory and invasive potential but decreased growth and proliferation in vitro and in vivo. CONCLUSION. AGR2 enhances the invasion phenotype of prostate cancer cells while at the same time attenuating cell-cycle progression. This function, its expression pattern and the increased level of AGR transcripts in urine sediments of prostate cancer patients call for further exploration as a prostate cancer marker and a modulator of tumor growth and invasion. Prostate 71: 575-587, 2011. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:575 / 587
页数:13
相关论文
共 39 条
[1]   Anterior specification of embryonic ectoderm:: the role of the Xenopus cement gland-specific gene XAG-2 [J].
Aberger, F ;
Weidinger, G ;
Grunz, H ;
Richter, K .
MECHANISMS OF DEVELOPMENT, 1998, 72 (1-2) :115-130
[2]   Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer [J].
Adam, PJ ;
Boyd, R ;
Tyson, KL ;
Fletcher, GC ;
Stamps, A ;
Hudson, L ;
Poyser, HR ;
Redpath, N ;
Griffiths, M ;
Steers, G ;
Harris, AL ;
Patel, S ;
Berry, J ;
Loader, JA ;
Townsend, RR ;
Daviet, L ;
Legrain, P ;
Parekh, R ;
Terrett, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (08) :6482-6489
[3]   The Metastasis-Associated Anterior Gradient 2 Protein Is Correlated with Poor Survival of Breast Cancer Patients [J].
Barraclough, Dong L. ;
Platt-Higgins, Angela ;
Rudland, Suzete de Silva ;
Barraclough, Roger ;
Winstanley, John ;
West, Christopher R. ;
Rudland, Philip S. .
AMERICAN JOURNAL OF PATHOLOGY, 2009, 175 (05) :1848-1857
[4]   Tyrol Prostate Cancer Demonstration Project: Early detection, treatment, outcome, incidence and mortality [J].
Bartsch, Georg ;
Horninger, Wolfgang ;
Klocker, Helmut ;
Pelzer, Alexandre ;
Bektic, Jasmin ;
Oberaigner, Wilhelm ;
Schennach, Harald ;
Schaefer, Georg ;
Frauscher, Ferdinand ;
Boniol, Mathieu ;
Severi, Gianluca ;
Robertson, Chris ;
Boyle, Peter .
BJU INTERNATIONAL, 2008, 101 (07) :809-816
[5]   CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis [J].
Baumann, P ;
Cremers, N ;
Kroese, FGM ;
Orend, G ;
Chiquet-Ehrismann, R ;
Uede, T ;
Yagita, H ;
Sleeman, JP .
CANCER RESEARCH, 2005, 65 (23) :10783-10793
[6]   hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan [J].
Fletcher, GC ;
Patel, S ;
Tyson, K ;
Adam, PJ ;
Schenker, M ;
Loader, JA ;
Daviet, L ;
Legrain, P ;
Parekh, R ;
Harris, AL ;
Terrett, JA .
BRITISH JOURNAL OF CANCER, 2003, 88 (04) :579-585
[7]  
Fritzsche FR, 2007, HISTOL HISTOPATHOL, V22, P703, DOI 10.14670/HH-22.703
[8]   Prognostic relevance of AGR2 expression in breast cancer [J].
Fritzsche, FR ;
Dah, E ;
Pahl, S ;
Burkhardt, M ;
Lu, J ;
Mayordomo, E ;
Gansukh, T ;
Dankof, A ;
Knuechel, R ;
Denkert, C ;
Winzer, KJ ;
Dietel, M ;
Kristiansen, G .
CLINICAL CANCER RESEARCH, 2006, 12 (06) :1728-1734
[9]   Use of oesophageal stress response proteins as potential biomarkers in the screening for Barrett's oesophagus [J].
Groome, Maximillian ;
Lindsay, Jamie ;
Ross, Peter E. ;
Cotton, James P. ;
Hupp, Ted R. ;
Dillon, John F. .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 2008, 20 (10) :961-965
[10]   Significance of the metastasis-inducing protein AGR2 for outcome in hormonally treated breast cancer patients [J].
Innes, HE ;
Liu, D ;
Barraclough, R ;
Davies, MPA ;
O'Neill, PA ;
Platt-Higgins, A ;
Rudland, SD ;
Sibson, DR ;
Rudland, PS .
BRITISH JOURNAL OF CANCER, 2006, 94 (07) :1057-1065