The anterior gradient 2 (AGR2) gene is overexpressed in prostate cancer and may be useful as a urine sediment marker for prostate cancer detection

Prostate - Tập 71 Số 6 - Trang 575-587 - 2011
Hui Bu1, Stefanie Bormann2, Georg Schäfer1, Wolfgang Horninger1, Petra Massoner1, Antje Neeb2, Vinoth‐Kumar Lakshmanan2, Danilo Maddalo2, Andrea Nestl2, Holger Sültmann3, Andrew C.B. Cato2, Helmut Klocker1
1Department of Urology, Division of Experimental Urology, Innsbruck Medical University, Innsbruck, Austria
2Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Eggenstein-Leopoldshafen, Germany
3German Cancer Research Center, Working Group Cancer Genome Research, Heidelberg, Germany

Tóm tắt

AbstractBACKGROUNDAGR2 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.METHODSUsing 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.RESULTSAGR2 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 %freePSA. 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.CONCLUSIONAGR2 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. © 2010 Wiley‐Liss, Inc.

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Prostate

Tập 71 Số 6

575-587

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