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 %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.
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.
Copyright © 2010 Wiley-Liss, Inc.