Anterior gradient protein 3 is associated with less aggressive tumors and better outcome of breast cancer patients
Status PubMed-not-MEDLINE Jazyk angličtina Země Nový Zéland Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
26170690
PubMed Central
PMC4485854
DOI
10.2147/ott.s82235
PII: ott-8-1523
Knihovny.cz E-zdroje
- Klíčová slova
- AGR3, ER-positive breast cancer, immuno histochemistry, patient survival, protein disulfide isomerase,
- Publikační typ
- časopisecké články MeSH
Anterior gradient protein (AGR) 3 is a highly related homologue of pro-oncogenic AGR2 and belongs to the family of protein disulfide isomerases. Although AGR3 was found in breast, ovary, prostate, and liver cancer, it remains of yet poorly defined function in tumorigenesis. This study aimed to determine AGR3 expression in a cohort of 129 primary breast carcinomas and evaluate the clinical and prognostic significance of AGR3 in these tumors. The immunohistochemical analysis revealed the presence of AGR3 staining to varying degrees in 80% of analyzed specimens. The percentage of AGR3-positive cells significantly correlated with estrogen receptor, progesterone receptor (both P<0.0001) as well as low histological grade (P=0.003), and inversely correlated with the level of Ki-67 expression (P<0.0001). In the whole cohort, AGR3 expression was associated with longer progression-free survival (PFS), whereas AGR3-positive subgroup of low-histological grade tumors showed both significantly longer PFS and overall survival. In conclusion, AGR3 is associated with the level of differentiation, slowly proliferating tumors, and more favorable prognosis of breast cancer patients.
Department of Pathology Masaryk Memorial Cancer Institute Brno Czech Republic
Regional Centre for Applied Molecular Oncology Brno Czech Republic
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Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–1403. PubMed
Sive HL, Hattori K, Weintraub H. Progressive determination during formation of the anteroposterior axis in Xenopus laevis. Cell. 1989;58(1):171–180. PubMed
Ivanova AS, Tereshina MB, Ermakova GV, Belousov VV, Zaraisky AG. Agr genes, missing in amniotes, are involved in the body appendages regeneration in frog tadpoles. Sci Rep. 2013;3:1279. PubMed PMC
Hatahet F, Ruddock LW. Protein disulfide isomerase: a critical evaluation of its function in disulfide bond formation. Antioxid Redox Signal. 2009;11(11):2807–2850. PubMed
Thompson DA, Weigel RJ. hAG-2, the human homologue of the Xenopus laevis cement gland gene XAG-2, is coexpressed with estrogen receptor in breast cancer cell lines. Biochem Biophys Res Commun. 1998;251(1):111–116. PubMed
Wilson CL, Sims AH, Howell A, Miller CJ, Clarke RB. Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue. Endocr Relat Cancer. 2006;13(2):617–628. PubMed
Fletcher GC, Patel S, Tyson K, et al. hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan. Br J Cancer. 2003;88(4):579–585. PubMed PMC
Innes HE, Liu D, Barraclough R, et al. Significance of the metastasis-inducing protein AGR2 for outcome in hormonally treated breast cancer patients. Br J Cancer. 2006;94(7):1057–1065. PubMed PMC
Barraclough DL, Platt-Higgins A, de Silva Rudland S, et al. The metastasis-associated anterior gradient 2 protein is correlated with poor survival of breast cancer patients. Am J Pathol. 2009;175(5):1848–1857. PubMed PMC
Hrstka R, Nenutil R, Fourtouna A, et al. The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers. Oncogene. 2010;29(34):4838–4847. PubMed
Fullwood MJ, Liu MH, Pan YF, et al. An oestrogen-receptor-alpha-bound human chromatin interactome. Nature. 2009;462(7269):58–64. PubMed PMC
Welboren WJ, van Driel MA, Janssen-Megens EM, et al. ChIP-Seq of ERalpha and RNA polymerase II defines genes differentially responding to ligands. EMBO J. 2009;28(10):1418–1428. PubMed PMC
Verma S, Salmans ML, Geyfman M, et al. The estrogen-responsive Agr2 gene regulates mammary epithelial proliferation and facilitates lobuloalveolar development. Dev Biol. 2012;369(2):249–260. PubMed PMC
Vanderlaag KE, Hudak S, Bald L, et al. Anterior gradient-2 plays a critical role in breast cancer cell growth and survival by modulating cyclin D1, estrogen receptor-alpha and survivin. Breast Cancer Res. 2010;12(3):R32. PubMed PMC
Liu D, Rudland PS, Sibson DR, Platt-Higgins A, Barraclough R. Human homologue of cement gland protein, a novel metastasis inducer associated with breast carcinomas. Cancer Res. 2005;65(9):3796–3805. PubMed
Adam PJ, Boyd R, Tyson KL, et al. Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer. J Biol Chem. 2003;278(8):6482–6489. PubMed
Petek E, Windpassinger C, Egger H, Kroisel PM, Wagner K. Localization of the human anterior gradient-2 gene (AGR2) to chromosome band 7p21.3 by radiation hybrid mapping and fluorescencein situ hybridisation. Cytogenet Cell Genet. 2000;89(3–4):141–142. PubMed
Brychtova V, Zampachova V, Hrstka R, et al. Differential expression of anterior gradient protein 3 in intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Exp Mol Pathol. 2014;96(3):375–381. PubMed
Gray TA, MacLaine NJ, Michie CO, et al. Anterior gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models. J Immunol Methods. 2012;378(1–2):20–32. PubMed
King ER, Tung CS, Tsang YT, et al. The anterior gradient homolog 3 (AGR3) gene is associated with differentiation and survival in ovarian cancer. Am J Surg Pathol. 2011;35(6):904–912. PubMed PMC
Vaarala MH, Hirvikoski P, Kauppila S, Paavonen TK. Identification of androgen-regulated genes in human prostate. Mol Med Rep. 2012;6(3):466–472. PubMed PMC
Bu H, Schweiger MR, Manke T, et al. Anterior gradient 2 and 3 – two prototype androgen-responsive genes transcriptionally upregulated by androgens and by oestrogens in prostate cancer cells. FEBS J. 2013;280(5):1249–1266. PubMed
Tavassoli FA, Devilee P. In: WHO Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. editors, editor. Lyon, France: IARC Press; 2003.
Sobin LH, Fleming ID. TNM classification of malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer. 1997;80(9):1803–1804. PubMed
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403–410. PubMed
Taiseer IR, Samar ARM, Abdelmonem HA. Immunohistochemical expression of aldehyde dehydrogenase-1 and hypoxia-inducible factor-1α in breast cancer. IJAR. 2014;2(7):822–830.
Brychtova V, Vojtesek B, Hrstka R. Anterior gradient 2: a novel player in tumor cell biology. Cancer Lett. 2011;304(1):1–7. PubMed
Chevet E, Fessart D, Delom F, et al. Emerging roles for the prooncogenic anterior gradient-2 in cancer development. Oncogene. 2013;32(20):2499–2509. PubMed
Salmans ML, Zhao F, Andersen B. The estrogen-regulated anterior gradient 2 (AGR2) protein in breast cancer: a potential drug target and biomarker. Breast Cancer Res. 2013;15(2):204. PubMed PMC
Fritzsche FR, Dahl E, Pahl S, et al. Prognostic relevance of AGR2 expression in breast cancer. Clin Cancer Res. 2006;12(6):1728–1734. PubMed
Smirnov DA, Zweitzig DR, Foulk BW, et al. Global gene expression profiling of circulating tumor cells. Cancer Res. 2005;65(12):4993–4997. PubMed
Hrstka R, Brychtova V, Fabian P, Vojtesek B, Svoboda M. AGR2 predicts tamoxifen resistance in postmenopausal breast cancer patients. Dis Markers. 2013;35(4):207–212. PubMed PMC
Darb-Esfahani S, Fritzsche F, Kristiansen G, et al. Anterior gradient protein 2 (AGR2) is an independent prognostic factor in ovarian high-grade serous carcinoma. Virchows Arch. 2012;461(2):109–116. PubMed
Park K, Chung YJ, So H, et al. AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and migration. Exp Mol Med. 2011;43(2):91–100. PubMed PMC
Hruz T, Laule O, Szabo G, et al. Genevestigator v3: a reference expression database for the meta-analysis of transcriptomes. Adv Bioinformatics. 2008;2008:420747. PubMed PMC
Obacz J, Takacova M, Brychtova V, et al. The role of AGR2 and AGR3 in cancer: similar but not identical. Eur J Cell Biol. 2015;94(3–4):139–147. PubMed
Norris AM, Gore A, Balboni A, Young A, Longnecker DS, Korc M. AGR2 is a SMAD4-suppressible gene that modulates MUC1 levels and promotes the initiation and progression of pancreatic intraepithelial neoplasia. Oncogene. 2013;32(33):3867–3876. PubMed PMC
Hrstka R, Murray E, Brychtova V, Fabian P, Hupp TR, Vojtesek B. Identification of an AKT-dependent signalling pathway that mediates tamoxifen-dependent induction of the pro-metastatic protein anterior gradient-2. Cancer Lett. 2013;333(2):187–193. PubMed
Tsuji T, Satoyoshi R, Aiba N, et al. Agr2 mediates paracrine effects on stromal fibroblasts that promote invasion by gastric signet-ring carcinoma cells. Cancer Res. 2015;75(2):356–366. PubMed
Arumugam T, Deng D, Bover L, Wang H, Logsdon CD, Ramachandran V. New blocking antibodies against novel AGR2-C4.4A pathway reduce growth and metastasis of pancreatic tumors and increase survival in mice. Mol Cancer Ther. 2015;14(4):941–951. PubMed PMC