The protein AGR2 is a putative member of the protein disulfide isomerase family and was first identified as a homolog of the Xenopus laevis gene XAG-2. AGR2 has been implicated in a number of human cancers. In particular, AGR2 has previously been found to be one of several genes that encode secreted proteins showing increased expression in prostate cancer cells compared to normal prostatic epithelium. Gene expression levels of AGR2 were examined in prostate cancer cells by microarray analysis. We further examined the relationship of AGR2 protein expression to histopathology and prostate cancer outcome on a population basis using tissue microarray technology. At the RNA and protein level, there was an increase in AGR2 expression in adenocarcinoma of the prostate compared to morphologically normal prostatic glandular epithelium. Using a tissue microarray, this enhanced AGR2 expression was seen as early as premalignant PIN lesions. Interestingly, within adenocarcinoma samples, there was a slight trend toward lower levels of AGR2 with increasing Gleason score. Consistent with this, relatively lower levels of AGR2 were highly predictive of disease recurrence in patients who had originally presented with high-stage primary prostate cancer (P = 0.009). We have shown for the first time that despite an increase in AGR2 expression in prostate cancer compared to non-malignant cells, relatively lower levels of AGR2 are highly predictive of disease recurrence following radical prostatectomy.
PubMed ID: 21144054
PMC ID: PMC3009682
Article link: BMC Cancer.
Grant support: CA111244 NCI NIH HHS , CA86366 NCI NIH HHS
Genes referenced: ag1 agr2 tbx2
Article Images: [+] show captions
|Figure 2. AGR2 immunohistochemistry. AGR2 staining was localized to the cytoplasm and membrane of cancer epithelial cells. (A) Tissue samples incubated with concentration-matched non-immune rabbit IgG showed no staining. Shown are representative sections of (B) morphologically normal tissue, (C) PIN, and (D) a representative adenocarcinoma (Gleason grade 7) showing low staining intensity, (E) a representative adenocarcinoma (Gleason grade 8) showing moderate staining intensity, and (F) a representative adenocarcinoma (Gleason grade 6) showing high staining intensity.|