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International Journal of Oncology
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Article

MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands

  • Authors:
    • Eun Joo Chung
    • Mary Ellen Urick
    • Naamit Kurshan
    • William Shield
    • Hiroaki Asano
    • Paul D. Smith
    • Bradley S. Scroggins
    • Jeffrey Burkeen
    • Deborah E. Citrin
  • View Affiliations / Copyright

    Affiliations: Section of Translational Radiation Oncology, Radiation Oncology Branch, National Institutes of Health, Bethesda, MD, USA, Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan, Cancer and Infection Research Area, AstraZeneca, Alderley Park, Macclesfield, UK
  • Pages: 2028-2036
    |
    Published online on: April 10, 2013
       https://doi.org/10.3892/ijo.2013.1890
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Abstract

The inhibition of the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway through the suppression of mutated Ras or MAPK/extracellular signal-regulated kinase 1/2 (MEK1/2) has been shown to sensitize tumor cells to ionizing radiation (IR). The molecular mechanisms of this sensitization however, are not yet fully understood. In this study, we investigated the role of transforming growth factor-α (TGF-α) in the radiosensitizing effects of selumetinib, a selective inhibitor of MEK1/2. The expression of epidermal growth factor receptor (EGFR) ligands was assessed by ELISA in both Ras wild-type and Ras mutant cells that were exposed to radiation with or without selumetinib. The effects of selumetinib on the TGF-α/EGFR signaling cascade in response to radiation were examined by western blot analysis, clonogenic assay and by determing the yield of mitotic catastrophe. The treatment of cells with selumetinib reduced the basal and IR-induced secretion of TGF-α in both Ras wild-type and Ras mutant cell lines in vitro and in vivo. The reduction of TGF-α secretion was accompanied with a reduction in phosphorylated tumor necrosis factor-α converting enzyme (TACE) in the cells treated with selumetinib with or without IR. The treatment of cells with selumetinib with or without IR inhibited the phosphorylation of EGFR and checkpoint kinase 2 (Chk2), and reduced the expression of survivin. Supplementation with exogenous TGF-α partially rescued the selumetinib-treated cells from IR-induced cell death, restored EGFR and Chk2 phosphorylation and increased survivin expression. These data suggest that the inhibition of MEK1/2 with selumetinib may provide a mechanism to sensitize tumor cells to IR in a fashion that prevents the activation of the TGF-α autocrine loop following IR.
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1 

Adamson ED: Oncogenes in development. Development. 99:449–471. 1987.

2 

Grander D: How do mutated oncogenes and tumor suppressor genes cause cancer? Med Oncol. 15:20–26. 1998. View Article : Google Scholar : PubMed/NCBI

3 

Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, MacConaill L, et al: High-throughput oncogene mutation profiling in human cancer. Nat Genet. 39:347–351. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Yarden Y: The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities. Eur J Cancer. 37:S3–S8. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Singh AB and Harris RC: Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal. 17:1183–1193. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Oliveira C, Velho S, Moutinho C, Ferreira A, Preto A, Domingo E, Capelinha AF, Duval A, Hamelin R, Machado JC, et al: KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression. Oncogene. 26:158–163. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Kumar R, Angelini S and Hemminki K: Activating BRAF and N-Ras mutations in sporadic primary melanomas: an inverse association with allelic loss on chromosome 9. Oncogene. 22:9217–9224. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, et al: Mutations of the BRAF gene in human cancer. Nature. 417:949–954. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Shigematsu H and Gazdar AF: Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer. 118:257–262. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Solit DB, Garraway LA, Pratilas CA, Sawai A, Getz G, Basso A, Ye Q, Lobo JM, She Y, Osman I, et al: BRAF mutation predicts sensitivity to MEK inhibition. Nature. 439:358–362. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Leboeuf R, Baumgartner JE, Benezra M, Malaguarnera R, Solit D, Pratilas CA, Rosen N, Knauf JA and Fagin JA: BRAFV600E mutation is associated with preferential sensitivity to mitogen-activated protein kinase kinase inhibition in thyroid cancer cell lines. J Clin Endocrinol Metab. 93:2194–2201. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Davies BR, Logie A, McKay JS, Martin P, Steele S, Jenkins R, Cockerill M, Cartlidge S and Smith PD: AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther. 6:2209–2219. 2007.

13 

Pohl G, Ho CL, Kurman RJ, Bristow R, Wang TL and Shih IeM: Inactivation of the mitogen-activated protein kinase pathway as a potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations. Cancer Res. 65:1994–2000. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Dry JR, Pavey S, Pratilas CA, Harbron C, Runswick S, Hodgson D, Chresta C, McCormack R, Byrne N, Cockerill M, et al: Transcriptional pathway signatures predict MEK addiction and response to selumetinib (AZD6244). Cancer Res. 70:2264–2273. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Chung EJ, Brown AP, Asano H, Mandler M, Burgan WE, Carter D, Camphausen K and Citrin D: In vitro and in vivo radiosensitization with AZD6244 (ARRY-142886), an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinase. Clin Cancer Res. 15:3050–3057. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Hagan M, Yacoub A and Dent P: Ionizing radiation causes a dose-dependent release of transforming growth factor alpha in vitro from irradiated xenografts and during palliative treatment of hormone-refractory prostate carcinoma. Clin Cancer Res. 10:5724–5731. 2004. View Article : Google Scholar

17 

Dent P, Reardon DB, Park JS, Bowers G, Logsdon C, Valerie K and Schmidt-Ullrich R: Radiation-induced release of transforming growth factor alpha activates the epidermal growth factor receptor and mitogen-activated protein kinase pathway in carcinoma cells, leading to increased proliferation and protection from radiation-induced cell death. Mol Biol Cell. 10:2493–2506. 1999.

18 

Dent P, Yacoub A, Fisher PB, Hagan MP and Grant S: MAPK pathways in radiation responses. Oncogene. 22:5885–5896. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Cengel KA, Voong KR, Chandrasekaran S, Maggiorella L, Brunner TB, Stanbridge E, Kao GD, McKenna WG and Bernhard EJ: Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells. Neoplasia. 9:341–348. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Castedo M, Perfettini JL, Roumier T, Andreau K, Medema R and Kroemer G: Cell death by mitotic catastrophe: a molecular definition. Oncogene. 23:2825–2837. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Grana TM, Sartor CI and Cox AD: Epidermal growth factor receptor autocrine signaling in RIE-1 cells transformed by the Ras oncogene enhances radiation resistance. Cancer Res. 63:7807–7814. 2003.PubMed/NCBI

22 

Borrell-Pages M, Rojo F, Albanell J, Baselga J and Arribas J: TACE is required for the activation of the EGFR by TGF-alpha in tumors. EMBO J. 22:1114–1124. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Lee DC, Sunnarborg SW, Hinkle CL, Myers TJ, Stevenson MY, Russell WE, Castner BJ, Gerhart MJ, Paxton RJ, Black RA, et al: TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase. Ann N Y Acad Sci. 995:22–38. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Rousseau S, Papoutsopoulou M, Symons A, Cook D, Lucocq JM, Prescott AR, O’Garra A, Ley SC and Cohen P: TPL2-mediated activation of ERK1 and ERK2 regulates the processing of pre-TNF alpha in LPS-stimulated macrophages. J Cell Sci. 121:149–154. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Gomez MI, Seaghdha MO and Prince AS: Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling. EMBO J. 26:701–709. 2007. View Article : Google Scholar

26 

Otaki M, Hatano M, Kobayashi K, Ogasawara T, Kuriyama T and Tokuhisa T: Cell cycle-dependent regulation of TIAP/msurvivin expression. Biochim Biophys Acta. 1493:188–194. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Castedo M, Perfettini JL, Roumier T, Yakushijin K, Horne D, Medema R and Kroemer G: The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe. Oncogene. 23:4353–4361. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Valerie K and Povirk LF: Regulation and mechanisms of mammalian double-strand break repair. Oncogene. 22:5792–5812. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Ward JF, Joner EI and Blakely WF: Effects of inhibitors of DNA strand break repair on HeLa cell radiosensitivity. Cancer Res. 44:59–63. 1984.PubMed/NCBI

30 

Toulany M, Dittmann K, Kruger M, Baumann M and Rodemann HP: Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway. Radiother Oncol. 76:143–150. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Martinez-Lacaci I, Kannan S, De Santis M, Bianco C, Kim N, Wallace-Jones B, Ebert AD, Wechselberger C and Salomon DS: RAS transformation causes sustained activation of epidermal growth factor receptor and elevation of mitogen-activated protein kinase in human mammary epithelial cells. Int J Cancer. 88:44–52. 2000. View Article : Google Scholar

32 

Horne MM and Guadagno TM: A requirement for MAP kinase in the assembly and maintenance of the mitotic spindle. J Cell Biol. 161:1021–1028. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Rainey MD, Black EJ, Zachos G and Gillespie DA: Chk2 is required for optimal mitotic delay in response to irradiation-induced DNA damage incurred in G2 phase. Oncogene. 27:896–906. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Lopergolo A, Tavecchio M, Lisanti S, Ghosh JC, Dohi T, Faversani A, Vaira V, Bosari S, Tanigawa N, Delia D, Kossenkov AV, Showe LC and Altieri DC: Chk2 phosphorylation of survivin-DeltaEx3 contributes to a DNA damage-sensing checkpoint in cancer. Cancer Res. 72:3251–3259. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Ghosh JC, Dohi T, Raskett CM, Kowalik TF and Altieri DC: Activated checkpoint kinase 2 provides a survival signal for tumor cells. Cancer Res. 66:11576–11579. 2006. View Article : Google Scholar : PubMed/NCBI

36 

Shi X, Wang D, Ding K, Lu Z, Jin Y, Zhang J and Pan J: GDP366, a novel small molecule dual inhibitor of survivin and Op18, induces cell growth inhibition, cellular senescence and mitotic catastrophe in human cancer cells. Cancer Biol Ther. 9:640–650. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Asanuma H, Torigoe T, Kamiguchi K, Hirohashi Y, Ohmura T, Hirata K, Sato M and Sato N: Survivin expression is regulated by coexpression of human epidermal growth factor receptor 2 and epidermal growth factor receptor via phosphatidylinositol 3-kinase/AKT signaling pathway in breast cancer cells. Cancer Res. 65:11018–11025. 2005. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Chung EJ, Urick ME, Kurshan N, Shield W, Asano H, Smith PD, Scroggins BS, Burkeen J and Citrin DE: MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands. Int J Oncol 42: 2028-2036, 2013.
APA
Chung, E.J., Urick, M.E., Kurshan, N., Shield , W., Asano, H., Smith, P.D. ... Citrin, D.E. (2013). MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands. International Journal of Oncology, 42, 2028-2036. https://doi.org/10.3892/ijo.2013.1890
MLA
Chung, E. J., Urick, M. E., Kurshan, N., Shield , W., Asano, H., Smith, P. D., Scroggins, B. S., Burkeen, J., Citrin, D. E."MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands". International Journal of Oncology 42.6 (2013): 2028-2036.
Chicago
Chung, E. J., Urick, M. E., Kurshan, N., Shield , W., Asano, H., Smith, P. D., Scroggins, B. S., Burkeen, J., Citrin, D. E."MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands". International Journal of Oncology 42, no. 6 (2013): 2028-2036. https://doi.org/10.3892/ijo.2013.1890
Copy and paste a formatted citation
x
Spandidos Publications style
Chung EJ, Urick ME, Kurshan N, Shield W, Asano H, Smith PD, Scroggins BS, Burkeen J and Citrin DE: MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands. Int J Oncol 42: 2028-2036, 2013.
APA
Chung, E.J., Urick, M.E., Kurshan, N., Shield , W., Asano, H., Smith, P.D. ... Citrin, D.E. (2013). MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands. International Journal of Oncology, 42, 2028-2036. https://doi.org/10.3892/ijo.2013.1890
MLA
Chung, E. J., Urick, M. E., Kurshan, N., Shield , W., Asano, H., Smith, P. D., Scroggins, B. S., Burkeen, J., Citrin, D. E."MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands". International Journal of Oncology 42.6 (2013): 2028-2036.
Chicago
Chung, E. J., Urick, M. E., Kurshan, N., Shield , W., Asano, H., Smith, P. D., Scroggins, B. S., Burkeen, J., Citrin, D. E."MEK1/2 inhibition enhances the radiosensitivity of cancer cells by downregulating survival and growth signals mediated by EGFR ligands". International Journal of Oncology 42, no. 6 (2013): 2028-2036. https://doi.org/10.3892/ijo.2013.1890
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