AGR2, an androgen-inducible secretory protein overexpressed in prostate cancer.
AGR2, the human homologue of Xenopus anterior gradient 2 (XAG2), was identified by a suppression subtractive hybridization-based technique as an androgen-inducible gene. There are two AGR2 transcripts, which encode the same secretory protein of 175 amino acids. The androgen induction was time- and dose-dependent, with more than a 10-fold increase in the level of AGR2 mRNA after 48 hr of treatment with 10(-9) M R1881. Expression of AGR2 mRNA was specifically detected in limited human tissue rich in epithelial cells, including the prostate gland. Analysis of 46 microdissected primary prostate adenocarcinoma samples showed that AGR2 mRNA expression was markedly elevated in the majority of tumors as compared to matched adjacent benign tissues. Androgen-induced AGR2 protein expression was demonstrated in LNCaP cells by Western blot analysis with an anti-AGR2 antibody. Immunohistochemistry analysis indicated that AGR2 protein expression was highly restricted to the secretory epithelial cells in the prostate gland. In tissue sections from radical prostatectomy specimens, immunohistochemical staining of AGR2 showed markedly increased expression in high-grade prostatic intraepithelial neoplasia and Gleason pattern 3-4 prostatic adenocarcinoma. Therefore, the androgen-induced secretory protein AGR2 may serve as a potential therapeutic target and/or molecular marker for prostate cancer.
Zhang
Jin-San
JS
Department of Urology, Mayo Clinic College of Medicine, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Gong
Aiyu
A
Cheville
John C
JC
Smith
David I
DI
Young
Charles Y F
CY
D000230:Adenocarcinoma / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D008969:Molecular Sequence Data; D009088:Mucoproteins; D015513:Oncogene Proteins; D011467:Prostate / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics*; D014176:Protein Biosynthesis; D019704:Protein Disulfide-Isomerases; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D045165:Testosterone Congeners / Q000494:pharmacology; D014158:Transcription, Genetic; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics
C502296:AGR2 protein, human; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D012333:RNA, Messenger; D045165:Testosterone Congeners; D029867:Xenopus Proteins; D015741:Metribolone; D019704:Protein Disulfide-Isomerases; C113451:XAG-2 protein, Xenopus