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Ahmad, Dena A. J.; Negm, Ola H.; Alabdullah, M. Layth; Mirza, Sameer; Hamed, Mohamed R.; Band, Vimla; Green, Andrew R.; Ellis, Ian O.; Rakha, Emad A. (2016)
Publisher: Springer US
Journal: Breast Cancer Research and Treatment
Languages: English
Types: Article
Subjects: Reverse phase protein microarray (RPPA), MAPK signalling pathways, Breast cancer, Preclinical Study, Cancer Research, Oncology
Background Mitogen-activated protein kinases (MAPKs) are signalling transduction molecules that have different functions and diverse behaviour in cancer. In breast cancer, MAPK is related to oestrogen receptor (ER) and HER2. Methods Protein expression of a large panel of MAPKs (JNK1/2, ERK, p38, C-JUN and ATF2 including phosphorylated forms) were assessed immunohistochemically in a large (n = 1400) and well-characterised breast cancer series prepared as tissue microarray. Moreover, reverse phase protein array was applied to quantify protein expression of MAPKs in six breast cancer cell lines with different phenotypes including HER2-transfected cells. Results MAPKs expression was associated with clinicopathological variables characteristic of good prognosis. These associations were most significant in the whole series and in the ER+ subgroup compared to other BC classes. Most of MAPKs showed a positive association with ER, BCL2 and better outcome and were negatively associated with the proliferation marker Ki67 and p53. Association of MAPK with HER2 was mainly seen in the ER- subgroup. Reverse phase protein array confirmed immunohistochemistry results and revealed differential expression of MAPK proteins in ER+ and ER− cell lines. Conclusions MAPKs are associated with good prognosis and their expression is mainly related to ER. Studying a large panel rather than individual biomarkers may provide improved understanding of the pathway. Electronic supplementary material The online version of this article (doi:10.1007/s10549-016-3967-9) contains supplementary material, which is available to authorized users.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Dhillon AS et al (2007) MAP kinase signalling pathways in cancer. Oncogene 26(22):3279-3290
    • 2. McCubrey JA et al (2007) Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 1773(8):1263-1284
    • 3. Chappell WH et al (2011) Ras/Raf/MEK/ERK and PI3K/PTEN/ Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget 2(3):135-164
    • 4. Neel NF et al (2011) The RalGEF-Ral effector signaling network: the road less traveled for anti-ras drug discovery. Genes Cancer 2(3):275-287
    • 5. Rajalingam K et al (2007) Ras oncogenes and their downstream targets. Biochim Biophys Acta 1773(8):1177-1195
    • 6. Ramos JW (2008) The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells. Int J Biochem Cell Biol 40(12):2707-2719
    • 7. Johannessen CM et al (2010) COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468(7326):968-972
    • 8. Schaeffer HJ, Weber MJ (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 19(4):2435-2444
    • 9. Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81(2):807-869
    • 10. Karin M, Gallagher E (2005) From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance. IUBMB Life 57(4-5):283-295
    • 11. Weston CR, Davis RJ (2007) The JNK signal transduction pathway. Curr Opin Cell Biol 19(2):142-149
    • 12. Merlin JL et al (2013) Expression and activation of P38 MAP kinase in invasive ductal breast cancers: correlation with expression of the estrogen receptor, HER2 and downstream signaling phosphorylated proteins. Oncol Rep 30(4):1943-1948
    • 13. Huang L et al (2013) Prognostic and predictive value of Phosphop44/42 and pAKT in HER2-positive locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy. World J Surg Oncol 11:307
    • 14. Kuo HT et al (2013) High nuclear phosphorylated extracellular signal-regulated kinase expression associated with poor differentiation, larger tumor size, and an advanced stage of breast cancer. Pol J Pathol 64(3):163-169
    • 15. McShane LM et al (2006) Reporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100(2):229-235
    • 16. Rakha EA et al (2008) Invasive lobular carcinoma of the breast: response to hormonal therapy and outcomes. Eur J Cancer 44(1):73-83
    • 17. AbdEl-Rehim DM et al (2005) High-throughput protein expression analysis using tissue microarray technology of a large wellcharacterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer 116(3):340-350
    • 18. AbdEl-Rehim DM et al (2004) Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma. Br J Cancer 91(8):1532-1542
    • 19. Rakha EA et al (2006) Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer 42(18):3149-3156
    • 20. Rakha EA et al (2006) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25-32
    • 21. Rakha EA et al (2007) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25-32
    • 22. Jerjees DA et al (2015) The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways. Breast Cancer Res Treat 150(1):91-103
    • 23. Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bioinformatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10(21):7252-7259
    • 24. Dimri M et al (2007) Modeling breast cancer-associated c-Src and EGFR overexpression in human MECs: c-Src and EGFR cooperatively promote aberrant three-dimensional acinar structure and invasive behavior. Cancer Res 67(9):4164-4172
    • 25. Negm OH et al (2014) A pro-inflammatory signalome is constitutively activated by C33Y mutant TNF receptor 1 in TNF receptor-associated periodic syndrome (TRAPS). Eur J Immunol 44(7):2096-2110
    • 26. Alshareeda AT et al (2014) SUMOylation proteins in breast cancer. Breast Cancer Res Treat 144(3):519-530
    • 27. Aleskandarany MA et al (2014) Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study. Breast Cancer Res Treat 145(2):339-348
    • 28. Mannsperger HA et al (2010) RPPanalyzer: analysis of reversephase protein array data. Bioinformatics 26(17):2202-2203
    • 29. Reddy KB et al (1999) Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells. Int J Cancer 82(2):268-273
    • 30. Liu QH et al (2015) Role of the ERK1/2 pathway in tumor chemoresistance and tumor therapy. Bioorg Med Chem Lett 25(2):192-197
    • 31. Neuzillet C et al (2014) MEK in cancer and cancer therapy. Pharmacol Ther 141(2):160-171
    • 32. Milde-Langosch K et al (2005) Expression and prognostic relevance of activated extracellular-regulated kinases (ERK1/2) in breast cancer. Br J Cancer 92(12):2206-2215
    • 33. Hsu YL et al (2005) Asiatic acid, a triterpene, induces apoptosis and cell cycle arrest through activation of extracellular signalregulated kinase and p38 mitogen-activated protein kinase pathways in human breast cancer cells. J Pharmacol Exp Ther 313(1):333-344
    • 34. Mamay CL et al (2003) An inhibitory function for JNK in the regulation of IGF-I signaling in breast cancer. Oncogene 22(4):602-614
    • 35. Altiok N, Koyuturk M, Altiok S (2007) JNK pathway regulates estradiol-induced apoptosis in hormone-dependent human breast cancer cells. Breast Cancer Res Treat 105(3):247-254
    • 36. Yu JH et al (2008) Protein tyrosine kinase, JNK, and ERK involvement in pseudolaric acid B-induced apoptosis of human breast cancer MCF-7 cells. Acta Pharmacol Sin 29(9):1069-1076
    • 37. Cocolakis E et al (2001) The p38 MAPK pathway is required for cell growth inhibition of human breast cancer cells in response to activin. J Biol Chem 276(21):18430-18436
    • 38. Kamaraju AK, Roberts AB (2005) Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-beta-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo. J Biol Chem 280(2):1024-1036
    • 39. Fister S et al (2009) GnRH-II antagonists induce apoptosis in human endometrial, ovarian, and breast cancer cells via activation of stress-induced MAPKs p38 and JNK and proapoptotic protein Bax. Cancer Res 69(16):6473-6481
    • 40. Reshkin SJ et al (2003) Paclitaxel induces apoptosis via protein kinase A- and p38 mitogen-activated protein-dependent inhibition of the Na?/H? exchanger (NHE) NHE isoform 1 in human breast cancer cells. Clin Cancer Res 9(6):2366-2373
    • 41. Bhoumik A, Ronai Z (2008) ATF2: A transcription factor that elicits oncogenic or tumor suppressor activities. Cell Cycle 7(15):2341-2345
    • 42. Maekawa T et al (2008) ATF-2 controls transcription of Maspin and GADD45 alpha genes independently from p53 to suppress mammary tumors. Oncogene 27(8):1045-1054
    • 43. Rudraraju B et al (2014) Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer. Breast Cancer Res Treat 147(2):295-309
    • 44. Knippen S et al (2009) Expression and prognostic value of activating transcription factor 2 (ATF2) and its phosphorylated form in mammary carcinomas. Anticancer Res 29(1):183-189
    • 45. Busch S et al (2012) Low ERK phosphorylation in cancer-associated fibroblasts is associated with tamoxifen resistance in premenopausal breast cancer. PLoS One 7(9):e45669
    • 46. Oh AS et al (2001) Hyperactivation of MAPK induces loss of ERalpha expression in breast cancer cells. Mol Endocrinol 15(8):1344-1359
    • 47. Ostrakhovitch EA, Cherian MG (2005) Inhibition of extracellular signal regulated kinase (ERK) leads to apoptosis inducing factor (AIF) mediated apoptosis in epithelial breast cancer cells: the lack of effect of ERK in p53 mediated copper induced apoptosis. J Cell Biochem 95(6):1120-1134
    • 48. Chen L et al (2009) Inhibition of the p38 kinase suppresses the proliferation of human ER-negative breast cancer cells. Cancer Res 69(23):8853-8861
    • 49. Creighton CJ et al (2006) Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors. Cancer Res 66(7):3903-3911
    • 50. Atanaskova N et al (2002) MAP kinase/estrogen receptor crosstalk enhances estrogen-mediated signaling and tumor growth but does not confer tamoxifen resistance. Oncogene 21(25):4000-4008
    • 51. Cagnol S, Chambard JC (2010) ERK and cell death: mechanisms of ERK-induced cell death-apoptosis, autophagy and senescence. FEBS J 277(1):2-21
    • 52. Subramaniam S, Unsicker K (2010) ERK and cell death: eRK1/2 in neuronal death. FEBS J 277(1):22-29
    • 53. Mebratu Y, Tesfaigzi Y (2009) How ERK1/2 activation controls cell proliferation and cell death: is subcellular localization the answer? Cell Cycle 8(8):1168-1175
    • 54. Courtois-Cox S et al (2006) A negative feedback signaling network underlies oncogene-induced senescence. Cancer Cell 10(6):459-472
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