Disease relevance of AGR2

• 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 [1].
• AGR2, an androgen-inducible secretory protein overexpressed in prostate cancer [1].
• 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 [1].
• Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease [2].
• Screening of breast tumor specimens using reverse transcription-PCR and immunocytochemistry with affinity-purified anti-AGR2 antibodies showed that the presence of AGR2 mRNA and protein were both statistically significantly associated with ERalpha-positive carcinomas (P = 0.007, Fisher's exact test) and with malignancy (P < or = 0.025) [3].

High impact information on AGR2

• These experiments are the first to link mechanistically the developmental gene product, AGR2, with metastasis in vivo [3].
• When an expression vector for AGR2 cDNA was introduced into benign nonmetastatic rat mammary tumor cells, and three separate clones and two pools of cells were transferred to the mammary glands of syngeneic hosts, there were no consistent differences in the mean latent periods of tumor formation [3].
• In contrast, PPARgamma-selective targets included genes linked to growth regulatory pathways (regenerating gene IA), colon epithelial cell maturation (GOB-4 and keratin 20), and immune modulation (neutrophil-gelatinase-associated lipocalin) [4].
• RESULTS: Immunohistochemical detection of AGR2 was statistically significantly associated with positive estrogen receptor status and lower tumor grade [5].
• AGR2 was over-expressed in 89% of prostate carcinomas, but did not have prognostic significance [6].

Biological context of AGR2

• Localization of the human anterior gradient-2 gene (AGR2) to chromosome band 7p21.3 by radiation hybrid mapping and fluorescencein situ hybridisation [7].
• Although the roles of hAG-2 and hAG-3 in mammalian cells are unknown, both proteins share a high degree of protein sequence homology and lie adjacent to one another on chromosome 7p21. hAG-2 mRNA expression has previously been demonstrated in oestrogen receptor (ER)-positive cell lines [8].
• Sequence analysis of clones obtained from a human breast adenocarcinoma MCF7 cDNA library suggests that at least three mRNA transcripts, differing in their 3'-untranslated regions, are transcribed from the hAG-2 gene [9].
• Coexpression of hAG-2 with ER suggests that hAG-2 may be involved in the tumor biology specific to the well-differentiated phenotype of hormonally-responsive breast cancers [9].
• Glycoproteins (GPs) in cyst fluid purified from the 2 genotypes of T. solium were characterized and compared with the recombinant chimeric T. solium-Ag1V1/Ag2 protein (Rec-Ag1V1/Ag2) as serodiagnostic antigens [10].

Anatomical context of AGR2

• Expression of AGR2 mRNA was specifically detected in limited human tissue rich in epithelial cells, including the prostate gland [1].
• On the basis of these analyses, we predict that a prepro-Ag2 undergoes a post-translational modification to yield the mature glycosylated Ag2 protein which is anchored on the extracellular plasma membrane of mycelial and spherule-phase cells [11].

Associations of AGR2 with chemical compounds

• 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 [1].
• Isolated mutants were further selected in 6-thioguanine-containing medium, and two mutant clones were finally obtained (AG1 and AG2) [12].
• Two Atlantic salmon AG-2 mRNA transcripts, designated asAG-2/1 and asAG-2/2, were cloned, sequenced, and shown to be predominantly expressed in the gill, intestine, and brain of a healthy fish [13].

Other interactions of AGR2

• Therefore, the androgen-induced secretory protein AGR2 may serve as a potential therapeutic target and/or molecular marker for prostate cancer [1].
• hAG-2 and hAG-3 are recently discovered human homologues of the secreted Xenopus laevis proteins XAG-1/2 (AGR-1/2) that are expressed in the cement gland, an ectodermal organ in the head associated with anteroposterior fate determination during early development [8].

Analytical, diagnostic and therapeutic context of AGR2

• Immunohistochemistry analysis indicated that AGR2 protein expression was highly restricted to the secretory epithelial cells in the prostate gland [1].
• Androgen-induced AGR2 protein expression was demonstrated in LNCaP cells by Western blot analysis with an anti-AGR2 antibody [1].
• However, metastases occurred in the lungs of animals receiving the AGR2 transfectants in 77% to 92% of animals with primary tumors (P = 0.0001) compared with no metastases in the control groups [3].
• Northern blot analyses identified two principal hAG-2 signals in all ER-positive breast carcinoma cell lines that were absent in cell lines not expressing, or minimally expressing, ER [9].

References