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The anterior gradient 2 (AGR2) gene is overexpressed in prostate cancer and may be useful as a urine sediment marker for prostate cancer detection.
- Source :
-
The Prostate [Prostate] 2011 May; Vol. 71 (6), pp. 575-87. Date of Electronic Publication: 2010 Oct 13. - Publication Year :
- 2011
-
Abstract
- 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.<br />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.<br />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.<br />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.<br /> (Copyright © 2010 Wiley-Liss, Inc.)
- Subjects :
- Animals
Biological Assay
Biomarkers, Tumor biosynthesis
Biomarkers, Tumor genetics
Cell Cycle genetics
Cohort Studies
Flow Cytometry
Gene Expression Regulation
Humans
Male
Mice
Mice, Nude
Mucoproteins
Neoplasms, Hormone-Dependent genetics
Neoplasms, Hormone-Dependent urine
Oncogene Proteins
Prostatic Neoplasms genetics
Prostatic Neoplasms urine
Proteins genetics
RNA, Neoplasm biosynthesis
RNA, Neoplasm genetics
Reverse Transcriptase Polymerase Chain Reaction
Statistics, Nonparametric
Transcription, Genetic
Transfection
Biomarkers, Tumor urine
Cell Cycle physiology
Neoplasms, Hormone-Dependent metabolism
Prostatic Neoplasms metabolism
Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0045
- Volume :
- 71
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Prostate
- Publication Type :
- Academic Journal
- Accession number :
- 20945500
- Full Text :
- https://doi.org/10.1002/pros.21273