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Article

MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells

  • Authors:
    • Sangmin Kim
    • Myeongjin Jeon
    • Jeong Eon Lee
    • Seok Jin Nam
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea
  • Pages: 2398-2404
    |
    Published online on: January 13, 2016
       https://doi.org/10.3892/or.2016.4557
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Abstract

Although tamoxifen reduces disease progression, tamoxifen resistance occurs during the course of estrogen receptor-positive [ER+] breast cancer treatment. In the present study, we investigated the possibility that interleukin-8 (IL-8) is a prognostic marker for tamoxifen resistance and aimed to clarify the regulation of IL-8 expression in tamoxifen-resistant cells. Clinically, IL-8 expression is positively correlated with survival in luminal A type breast cancer patients, but not in luminal B type breast cancer patients. In addition, the levels of IL-8 mRNA and protein expression were significantly increased in tamoxifen-resistant (TamR) cells compared to tamoxifen-sensitive (TamS) cells. To determine the regulatory mechanism of IL-8 expression in TamR cells, we analyzed the activities of signaling molecules. Our results showed that the phosphorylation levels of MEK and Akt were markedly increased in TamR cells, but there was no change in the phosphorylation level of p38 MAPK. On the contrary, we observed that elevated IL-8 mRNA expression was suppressed by a specific MEK1/2 inhibitor, UO126, but not by the specific PI-3K inhibitor LY294002, in TamR cells, whereas, we found that overexpression of constitutively active-MEK (CA-MEK) significantly increased the levels of IL-8 mRNA expression in TamS cells. Finally, we investigated the effect of the specific CXCR1/2 inhibitor SB225002 on anchorage-independent growth of TamR cells, and found that the growth was completely suppressed by SB225002. Taken together, our results demonstrate that IL-8 expression is regulated through a MEK/ERK-dependent pathway in TamR cells, suggesting that IL-8 and its receptors may be promising therapeutic targets for overcoming tamoxifen resistance.
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1 

Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Jordan VC and O'Malley BW: Selective estrogen-receptor modulators and antihormonal resistance in breast cancer. J Clin Oncol. 25:5815–5824. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Jordan VC and Murphy CS: Endocrine pharmacology of antiestrogens as antitumor agents. Endocr Rev. 11:578–610. 1990. View Article : Google Scholar : PubMed/NCBI

4 

Ring A and Dowsett M: Mechanisms of tamoxifen resistance. Endocr Relat Cancer. 11:643–658. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, et al Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials. Lancet. 378:771–784. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Kim S, Lee J, Oh SJ, Nam SJ and Lee JE: Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells. Oncol Rep. 34:1613–1619. 2015.PubMed/NCBI

7 

Maxwell PJ, Gallagher R, Seaton A, Wilson C, Scullin P, Pettigrew J, Stratford IJ, Williams KJ, Johnston PG and Waugh DJ: HIF-1 and NF-kappaB-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells. Oncogene. 26:7333–7345. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Collins TS, Lee LF and Ting JP: Paclitaxel up-regulates interleukin-8 synthesis in human lung carcinoma through an NF-kappaB- and AP-1-dependent mechanism. Cancer Immunol Immunother. 49:78–84. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Waugh DJ and Wilson C: The interleukin-8 pathway in cancer. Clin Cancer Res. 14:6735–6741. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Kassim SK, El-Salahy EM, Fayed ST, Helal SA, Helal T, Azzam ED and Khalifa A: Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients. Clin Biochem. 37:363–369. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Mayerhofer K, Bodner K, Bodner-Adler B, Schindl M, Kaider A, Hefler L, Zeillinger R, Leodolter S, Joura EA and Kainz C: Interleukin-8 serum level shift in patients with ovarian carcinoma undergoing paclitaxel-containing chemotherapy. Cancer. 91:388–393. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Miller LJ, Kurtzman SH, Wang Y, Anderson KH, Lindquist RR and Kreutzer DL: Expression of interleukin-8 receptors on tumor cells and vascular endothelial cells in human breast cancer tissue. Anticancer Res. 18(1A): 77–81. 1998.PubMed/NCBI

13 

Chavey C, Bibeau F, Gourgou-Bourgade S, Burlinchon S, Boissière F, Laune D, Roques S and Lazennec G: Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res. 9:R152007. View Article : Google Scholar : PubMed/NCBI

14 

Freund A, Chauveau C, Brouillet JP, Lucas A, Lacroix M, Licznar A, Vignon F and Lazennec G: IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells. Oncogene. 22:256–265. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Freund A, Jolivel V, Durand S, Kersual N, Chalbos D, Chavey C, Vignon F and Lazennec G: Mechanisms underlying differential expression of interleukin-8 in breast cancer cells. Oncogene. 23:6105–6114. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Martin D, Galisteo R and Gutkind JS: CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex. J Biol Chem. 284:6038–6042. 2009. View Article : Google Scholar :

17 

Li A, Varney ML, Valasek J, Godfrey M, Dave BJ and Singh RK: Autocrine role of interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production and angiogenesis. Angiogenesis. 8:63–71. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Knowlden JM, Hutcheson IR, Jones HE, Madden T, Gee JM, Harper ME, Barrow D, Wakeling AE and Nicholson RI: Elevated levels of epidermal growth factor receptor/c-erbB2 heterodimers mediate an autocrine growth regulatory pathway in tamoxifen-resistant MCF-7 cells. Endocrinology. 144:1032–1044. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Shi Z, Yang WM, Chen LP, Yang DH, Zhou Q, Zhu J, Chen JJ, Huang RC, Chen ZS and Huang RP: Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production. Breast Cancer Res Treat. 135:737–747. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Yang J, Wang Y, Gao Y, Shao J, Zhang XJ and Yao Z: Reciprocal regulation of 17beta-estradiol, interleukin-6 and interleukin-8 during growth and progression of epithelial ovarian cancer. Cytokine. 46:382–391. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Sansone P, Storci G, Giovannini C, Pandolfi S, Pianetti S, Taffurelli M, Santini D, Ceccarelli C, Chieco P and Bonafé M: p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres. Stem Cells. 25:807–815. 2007. View Article : Google Scholar

22 

Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, Clouthier SG and Wicha MS: Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol. 7:e10001212009. View Article : Google Scholar : PubMed/NCBI

23 

Rody A, Karn T, Liedtke C, Pusztai L, Ruckhaeberle E, Hanker L, Gaetje R, Solbach C, Ahr A, Metzler D, et al: A clinically relevant gene signature in triple negative and basal-like breast cancer. Breast Cancer Res. 13:R972011. View Article : Google Scholar : PubMed/NCBI

24 

Benoy IH, Salgado R, Van Dam P, Geboers K, Van Marck E, Scharpé S, Vermeulen PB and Dirix LY: Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival. Clin Cancer Res. 10:7157–7162. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Singh B, Berry JA, Vincent LE and Lucci A: Involvement of IL-8 in CoX-2-mediated bone metastases from breast cancer. J Surg Res. 134:44–51. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Singh JK, Simões BM, Howell SJ, Farnie G and Clarke RB: Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells. Breast Cancer Res. 15:2102013. View Article : Google Scholar : PubMed/NCBI

27 

Yuan A, Yang PC, Yu CJ, Chen WJ, Lin FY, Kuo SH and Luh KT: Interleukin-8 messenger ribonucleic acid expression correlates with tumor progression, tumor angiogenesis, patient survival, and timing of relapse in non-small-cell lung cancer. Am J Respir Crit Care Med. 162:1957–1963. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Xie K: Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev. 12:375–391. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Mukaida N, Okamoto S, Ishikawa Y and Matsushima K: Molecular mechanism of interleukin-8 gene expression. J Leukoc Biol. 56:554–558. 1994.PubMed/NCBI

30 

Scherle PA, Jones EA, Favata MF, Daulerio AJ, Covington MB, Nurnberg SA, Magolda RL and Trzaskos JM: Inhibition of MAP kinase kinase prevents cytokine and prostaglandin E2 production in lipopolysaccharide-stimulated monocytes. J Immunol. 161:5681–5686. 1998.PubMed/NCBI

31 

Aupperle K, Bennett B, Han Z, Boyle D, Manning A and Firestein G: NF-kappa B regulation by I kappa B kinase-2 in rheumatoid arthritis synoviocytes. J Immunol. 166:2705–2711. 2001. View Article : Google Scholar : PubMed/NCBI

32 

Sueoka H, Hirano T, Uda Y, Iimuro Y, Yamanaka J and Fujimoto J: Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma. Surgery. 155:640–649. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, et al: CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 120:485–497. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kim S, Jeon M, Lee JE and Nam SJ: MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells. Oncol Rep 35: 2398-2404, 2016.
APA
Kim, S., Jeon, M., Lee, J.E., & Nam, S.J. (2016). MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells. Oncology Reports, 35, 2398-2404. https://doi.org/10.3892/or.2016.4557
MLA
Kim, S., Jeon, M., Lee, J. E., Nam, S. J."MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells". Oncology Reports 35.4 (2016): 2398-2404.
Chicago
Kim, S., Jeon, M., Lee, J. E., Nam, S. J."MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells". Oncology Reports 35, no. 4 (2016): 2398-2404. https://doi.org/10.3892/or.2016.4557
Copy and paste a formatted citation
x
Spandidos Publications style
Kim S, Jeon M, Lee JE and Nam SJ: MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells. Oncol Rep 35: 2398-2404, 2016.
APA
Kim, S., Jeon, M., Lee, J.E., & Nam, S.J. (2016). MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells. Oncology Reports, 35, 2398-2404. https://doi.org/10.3892/or.2016.4557
MLA
Kim, S., Jeon, M., Lee, J. E., Nam, S. J."MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells". Oncology Reports 35.4 (2016): 2398-2404.
Chicago
Kim, S., Jeon, M., Lee, J. E., Nam, S. J."MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells". Oncology Reports 35, no. 4 (2016): 2398-2404. https://doi.org/10.3892/or.2016.4557
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