Cyclooxygenase-2 utilizes Jun N-terminal kinases to induce invasion, but not tamoxifen resistance, in MCF-7 breast cancer cells

Gonzalez-Villasana,Vianey; Gutiérrez-Puente,Yolanda; Tari,Ana  M.

doi:10.3892/or.2013.2549

Cyclooxygenase-2 utilizes Jun N-terminal kinases to induce invasion, but not tamoxifen resistance, in MCF-7 breast cancer cells

Authors:
- Vianey Gonzalez-Villasana
- Yolanda Gutiérrez-Puente
- Ana M. Tari
View Affiliations

Affiliations: Department of Biochemistry, Faculty of Biological Sciences, University of Nuevo Leon, San Nicolas de los Garza, Nuevo León, Mexico, Department of Neuroscience, University of Florida, Gainesville, FL, USA
Published online on: June 19, 2013 https://doi.org/10.3892/or.2013.2549
Pages: 1506-1510

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Elevated cyclooxygenase-2 (COX-2) expression in breast tumors is associated with a lower survival rate in patients with estrogen receptor α (ERα)-positive tumors. We hypothesized that COX-2 reduces the survival rate of breast cancer patients with ERα-positive tumors since COX-2 increases the invasiveness of ERα-positive breast tumors and decreases tumor sensitivity to tamoxifen. Previously, we demonstrated that COX-2 stimulates the activity of protein kinase C (PKC) to increase the invasiveness of ERα-positive MCF-7 breast cancer cells and to decrease the sensitivity of MCF-7 cells to tamoxifen. High levels of COX-2 are associated with the activation of the mitogen-activated protein kinase (MAPK) family and the Akt kinase. However, it is not known whether these kinases mediate COX-2-induced invasive activity and tamoxifen resistance. In the present study, we report that COX-2 utilizes PKC to enhance the phosphorylation of Jun N-terminal kinases (JNKs), but not that of other MAPK family members or Akt. Inhibition aimed at JNKs reduced COX-2-induced invasion but not COX-2-induced tamoxifen resistance. We conclude that JNKs are essential for induced cell invasion by COX-2, but not tamoxifen resistance, in ERα-positive breast cancer cells.

View Figures

View References

1	Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S and DuBois RN: Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 107:1183–1188. 1994.PubMed/NCBI
2	Soslow RA, Dannenberg AJ, Rush D, et al: COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer. 89:2637–2645. 2000. View Article : Google Scholar : PubMed/NCBI
3	Kirschenbaum A, Liu X, Yao S and Levine AC: The role of cyclooxygenase-2 in prostate cancer. Urology. 58:127–131. 2001. View Article : Google Scholar : PubMed/NCBI
4	Ristimaki A, Sivula A, Lundin J, et al: Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res. 62:632–635. 2002.PubMed/NCBI
5	Denkert C, Winzer KJ, Muller BM, et al: Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease-free survival and overall survival in patients with breast carcinoma. Cancer. 97:2978–2987. 2003. View Article : Google Scholar : PubMed/NCBI
6	O’Connor JK, Avent J, Lee RJ, Fischbach J and Gaffney DK: Cyclooxygenase-2 expression correlates with diminished survival in invasive breast cancer treated with mastectomy and radiotherapy. Int J Radiat Oncol Biol Phys. 58:1034–1040. 2004.PubMed/NCBI
7	Spizzo G, Gastl G, Wolf D, et al: Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survival. Br J Cancer. 88:574–578. 2003. View Article : Google Scholar : PubMed/NCBI
8	Surowiak P, Materna V, Matkowski R, et al: Relationship between the expression of cyclooxygenase 2 and MDR1/P-glycoprotein in invasive breast cancers and their prognostic significance. Breast Cancer Res. 7:R862–R870. 2005. View Article : Google Scholar : PubMed/NCBI
9	Holmes MD, Chen WY, Schnitt SJ, et al: COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin. Breast Cancer Res Treat. 130:657–662. 2011. View Article : Google Scholar : PubMed/NCBI
10	Tari AM, Simeone AM, Li YJ, Gutierrez-Puente Y, Lai S and Symmans WF: Cyclooxygenase-2 protein reduces tamoxifen and N-(4-hydroxyphenyl)retinamide inhibitory effects in breast cancer cells. Lab Invest. 85:1357–1367. 2005. View Article : Google Scholar : PubMed/NCBI
11	Costa C, Soares R, Reis-Filho J, Leitao D, Amendoeira I and Schmitt F: Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J Clin Pathol. 55:429–434. 2002. View Article : Google Scholar : PubMed/NCBI
12	Ranger GS, Thomas V, Jewell A and Mokbel K: Elevated cyclooxygenase-2 expression correlates with distant metastases in breast cancer. Anticancer Res. 24:2349–2351. 2004.PubMed/NCBI
13	Simeone AM, Nieves-Alicea R, McMurtry VC, Colella S, Krahe R and Tari AM: Cyclooxygenase-2 uses the protein kinase C/interleukin-8/urokinase-type plasminogen activator pathway to increase the invasiveness of breast cancer cells. Int J Oncol. 30:785–792. 2007.PubMed/NCBI
14	Prosperi JR, Mallery SR, Kigerl KA, Erfurt AA and Robertson FM: Invasive and angiogenic phenotype of MCF-7 human breast tumor cells expressing human cyclooxygenase-2. Prostaglandins Other Lipid Mediat. 73:249–264. 2004. View Article : Google Scholar : PubMed/NCBI
15	Singh B, Berry JA, Shoher A, Ramakrishnan V and Lucci A: COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol. 26:1393–1399. 2005.PubMed/NCBI
16	Connolly EM, Harmey JH, O’Grady T, et al: Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer. Br J Cancer. 87:231–237. 2002. View Article : Google Scholar : PubMed/NCBI
17	Kundu N and Fulton AM: Selective cyclooxygenase (COX)-1 or COX-2 inhibitors control metastatic disease in a murine model of breast cancer. Cancer Res. 62:2343–2346. 2002.PubMed/NCBI
18	Roche-Nagle G, Connolly EM, Eng M, Bouchier-Hayes DJ and Harmey JH: Antimetastatic activity of a cyclooxygenase-2 inhibitor. Br J Cancer. 91:359–365. 2004.PubMed/NCBI
19	Ogunwobi O, Mutungi G and Beales IL: Leptin stimulates proliferation and inhibits apoptosis in Barrett’s esophageal adenocarcinoma cells by cyclooxygenase-2-dependent, prostaglandin-E2-mediated transactivation of the epidermal growth factor receptor and c-Jun NH₂-terminal kinase activation. Endocrinology. 147:4505–4516. 2006.PubMed/NCBI
20	Leone V, di Palma A, Ricchi P, et al: PGE₂ inhibits apoptosis in human adenocarcinoma Caco-2 cell line through Ras-PI3K association and cAMP-dependent kinase A activation. Am J Physiol Gastrointest Liver Physiol. 293:G673–G681. 2007.PubMed/NCBI
21	Repasky GA, Zhou Y, Morita S and Der CJ: Ras-mediated intestinal epithelial cell transformation requires cyclooxygenase-2-induced prostaglandin E₂ signaling. Mol Carcinog. 46:958–970. 2007. View Article : Google Scholar : PubMed/NCBI
22	Zhang Z, Lai GH and Sirica AE: Celecoxib-induced apoptosis in rat cholangiocarcinoma cells mediated by Akt inactivation and Bax translocation. Hepatology. 39:1028–1037. 2004. View Article : Google Scholar : PubMed/NCBI
23	McMurtry V, Simeone AM, Nieves-Alicea R and Tari AM: Leptin utilizes Jun N-terminal kinases to stimulate the invasion of MCF-7 breast cancer cells. Clin Exp Metastasis. 26:197–204. 2008. View Article : Google Scholar : PubMed/NCBI
24	Gonzalez-Villasana V, Nieves-Alicea R, McMurtry V, Gutierrez-Puente Y and Tari AM: Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion. Oncol Rep. 27:861–866. 2012.PubMed/NCBI
25	Li Z, Xu X, Bai L, Chen W and Lin Y: Epidermal growth factor receptor-mediated tissue transglutaminase overexpression couples acquired tumor necrosis factor-related apoptosis-inducing ligand resistance and migration through c-FLIP and MMP-9 proteins in lung cancer cells. J Biol Chem. 286:21164–21172. 2011. View Article : Google Scholar
26	Nieves-Alicea R, Colburn NH, Simeone AM and Tari AM: Programmed cell death 4 inhibits breast cancer cell invasion by increasing tissue inhibitor of metalloproteinases-2 expression. Breast Cancer Res Treat. 114:203–209. 2008. View Article : Google Scholar : PubMed/NCBI
27	Wang J, Kuiatse I, Lee AV, Pan J, Giuliano A and Cui X: Sustained c-Jun-NH₂-kinase activity promotes epithelial-mesenchymal transition, invasion, and survival of breast cancer cells by regulating extracellular signal-regulated kinase activation. Mol Cancer Res. 8:266–277. 2010.
28	Davidson B, Konstantinovsky S, Kleinberg L, et al: The mitogen-activated protein kinases (MAPK) p38 and JNK are markers of tumor progression in breast carcinoma. Gynecol Oncol. 102:453–461. 2006. View Article : Google Scholar : PubMed/NCBI
29	Yeh YT, Hou MF, Chung YF, et al: Decreased expression of phosphorylated JNK in breast infiltrating ductal carcinoma is associated with a better overall survival. Int J Cancer. 118:2678–2684. 2006. View Article : Google Scholar : PubMed/NCBI
30	Johnston SR, Lu B, Scott GK, et al: Increased activator protein-1 DNA binding and c-Jun NH₂-terminal kinase activity in human breast tumors with acquired tamoxifen resistance. Clin Cancer Res. 5:251–256. 1999.PubMed/NCBI
31	Schiff R, Reddy P, Ahotupa M, et al: Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo. J Natl Cancer Inst. 92:1926–1934. 2000. View Article : Google Scholar : PubMed/NCBI
32	Garcia-Becerra R, Santos N, Diaz L and Camacho J: Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs and genetically based resistance. Int J Mol Sci. 14:108–145. 2012. View Article : Google Scholar : PubMed/NCBI
33	Sweeney EE, McDaniel RE, Maximov PY, Fan P and Jordan VC: Models and mechanisms of acquired antihormone resistance in breast cancer: significant clinical progress despite limitations. Horm Mol Biol Clin Investig. 9:143–163. 2012.PubMed/NCBI
34	Bianco S and Gevry N: Endocrine resistance in breast cancer: from cellular signaling pathways to epigenetic mechanisms. Transcription. 3:165–170. 2012. View Article : Google Scholar : PubMed/NCBI