AGR2 Predicts Tamoxifen Resistance in Postmenopausal Breast Cancer Patients

Overview

Journal Dis Markers

Publisher Wiley

Specialty Biochemistry

Date 2013 Oct 30

PMID 24167368

Citations 18

Authors

Roman Hrstka

Veronika Brychtova

Pavel Fabian

Borivoj Vojtesek

Marek Svoboda

Affiliations

Soon will be listed here.

Abstract

Endocrine resistance is a significant problem in breast cancer treatment. Thus identification and validation of novel resistance determinants is important to improve treatment efficacy and patient outcome. In our work, AGR2 expression was determined by qRT-PCR in Tru-Cut needle biopsies from tamoxifen-treated postmenopausal breast cancer patients. Our results showed inversed association of AGR2 mRNA levels with primary treatment response (P = 0.0011) and progression-free survival (P = 0.0366) in 61 ER-positive breast carcinomas. As shown by our experimental and clinical evaluations, elevated AGR2 expression predicts decreased efficacy of tamoxifen treatment. From this perspective, AGR2 is a potential predictive biomarker enabling selection of an optimal algorithm for adjuvant hormonal therapy in postmenopausal ER-positive breast cancer patients.

Citing Articles

Potential Role of AGR2 for Mammalian Skin Wound Healing.

Kosykh A, Tereshina M, Gurskaya N Int J Mol Sci. 2023; 24(9).

PMID: 37175601 PMC: 10178616. DOI: 10.3390/ijms24097895.

Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition.

Martisova A, Sommerova L, Krejci A, Selingerova I, Kolarova T, Zavadil Kokas F Int J Mol Sci. 2022; 23(18).

PMID: 36142758 PMC: 9504245. DOI: 10.3390/ijms231810845.

Molecular markers associated with the outcome of tamoxifen treatment in estrogen receptor-positive breast cancer patients: scoping review and in silico analysis.

Dal Berto M, Dos Santos G, Dos Santos A, Silva A, Vargas J, Alves R Discov Oncol. 2022; 12(1):37.

PMID: 35201456 PMC: 8777552. DOI: 10.1007/s12672-021-00432-7.

Inhibitory Effect of Etravirine, a Non-Nucleoside Reverse Transcriptase Inhibitor, via Anterior Gradient Protein 2 Homolog Degradation against Ovarian Cancer Metastasis.

Ly T, Yun J, Ha J, Kim Y, Jang W, Van Le T Int J Mol Sci. 2022; 23(2).

PMID: 35055132 PMC: 8777939. DOI: 10.3390/ijms23020944.

Anterior gradient protein 2 is a marker of tumor aggressiveness in breast cancer and favors chemotherapy‑induced senescence escape.

Maarouf A, Boissard A, Henry C, Leman G, Coqueret O, Guette C Int J Oncol. 2021; 60(1).

PMID: 34913074 PMC: 8727137. DOI: 10.3892/ijo.2021.5295.

References

Hengel S, Murray E, Langdon S, Hayward L, ODonoghue J, Panchaud A . Data-independent proteomic screen identifies novel tamoxifen agonist that mediates drug resistance. J Proteome Res. 2011; 10(10):4567-78. PMC: 3242698. DOI: 10.1021/pr2004117. View

Abd El-Rehim D, Ball G, Pinder S, Rakha E, Paish C, Robertson J . High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer. 2005; 116(3):340-50. DOI: 10.1002/ijc.21004. View

Hrstka R, Nenutil R, Fourtouna A, Maslon M, Naughton C, Langdon S . The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers. Oncogene. 2010; 29(34):4838-47. DOI: 10.1038/onc.2010.228. View

Robertson J, Cannon P, Nicholson R, Blamey R . Oestrogen and progesterone receptors as prognostic variables in hormonally treated breast cancer. Int J Biol Markers. 1996; 11(1):29-35. DOI: 10.1177/172460089601100106. View

Wang Z, Hao Y, Lowe A . The adenocarcinoma-associated antigen, AGR2, promotes tumor growth, cell migration, and cellular transformation. Cancer Res. 2008; 68(2):492-7. DOI: 10.1158/0008-5472.CAN-07-2930. View

Thompson D, Weigel R . 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):111-6. DOI: 10.1006/bbrc.1998.9440. View

Hodges L, Cook J, Lobenhofer E, Li L, Bennett L, Bushel P . Tamoxifen functions as a molecular agonist inducing cell cycle-associated genes in breast cancer cells. Mol Cancer Res. 2003; 1(4):300-11. View

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

Katzenellenbogen B, Frasor J . Therapeutic targeting in the estrogen receptor hormonal pathway. Semin Oncol. 2004; 31(1 Suppl 3):28-38. DOI: 10.1053/j.seminoncol.2004.01.004. View

10.

Arpino G, Green S, Allred D, Lew D, Martino S, Osborne C . HER-2 amplification, HER-1 expression, and tamoxifen response in estrogen receptor-positive metastatic breast cancer: a southwest oncology group study. Clin Cancer Res. 2004; 10(17):5670-6. DOI: 10.1158/1078-0432.CCR-04-0110. View

11.

Hrstka R, Murray E, Brychtova V, Fabian P, Hupp T, 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):187-93. DOI: 10.1016/j.canlet.2013.01.034. View

12.

Pohler E, Craig A, Cotton J, Lawrie L, Dillon J, Ross P . The Barrett's antigen anterior gradient-2 silences the p53 transcriptional response to DNA damage. Mol Cell Proteomics. 2004; 3(6):534-47. DOI: 10.1074/mcp.M300089-MCP200. View

13.

Liu D, Rudland P, Sibson D, Platt-Higgins A, Barraclough R . Human homologue of cement gland protein, a novel metastasis inducer associated with breast carcinomas. Cancer Res. 2005; 65(9):3796-805. DOI: 10.1158/0008-5472.CAN-04-3823. View

14.

Innes H, Liu D, Barraclough R, Davies M, ONeill P, Platt-Higgins A . Significance of the metastasis-inducing protein AGR2 for outcome in hormonally treated breast cancer patients. Br J Cancer. 2006; 94(7):1057-65. PMC: 2361240. DOI: 10.1038/sj.bjc.6603065. View

15.

Dong A, Gupta A, Pai R, Tun M, Lowe A . The human adenocarcinoma-associated gene, AGR2, induces expression of amphiregulin through Hippo pathway co-activator YAP1 activation. J Biol Chem. 2011; 286(20):18301-10. PMC: 3093902. DOI: 10.1074/jbc.M110.215707. View

16.

McCarty Jr K, Miller L, Cox E, Konrath J, McCarty Sr K . Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985; 109(8):716-21. View