Skip to main content

Advertisement

SpringerLink
Log in

Inhibiting ERp29 expression enhances radiosensitivity in human nasopharyngeal carcinoma cell lines

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

ERp29 is an endoplasmic reticulum (ER) stress-inducible protein. It was found that ERp29 was highly expressed in several cancers and associated with resistance to oxidative and radiation stress, which may serve as a novel target for nasopharyngeal carcinoma (NPC) anticancer approach. In this study, we used immunohistochemistry to detect ERp29 expression in radioresistant and radiosensitive NPC tissues. As a result, ERp29 was up-regulated in radioresistant NPC tissues compared to radiosensitive NPC tissues. We also found that ERp29 knockdown attenuated radioresistance of NPC CNE-1 cells and ERp29 overexpression enhanced radioresistance of NPC CNE-2 cells. When exposed to radiation, ERp29 knockdown CNE-1 cells increased radiation-induced cell apoptosis and ERp29 overexpression CNE-2 cells reduced radiation-induced cell apoptosis. Further, we demonstrated that ERp29 up-regulated the expression of Hsp27. In conclusion, our study supports ERp29 could potentiate resistance to radiation in NPC cells, targeting of ERp29 is a rational strategy in treating radioresistant NPC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Moenner M, Pluquet O, Bouchecareilh M, Chevet E. Integrated endoplasmic reticulum stress responses in cancer. Cancer Res. 2007;67:10631–4.

    Article  PubMed  CAS  Google Scholar 

  2. Ma Y, Hendershot LM. The role of the unfolded protein response in tumour development: friend or foe. Nat Rev Cancer. 2004;4:966–77.

    Article  PubMed  CAS  Google Scholar 

  3. Li J, Lee AS. Stress induction of GRP78/BiP and its role in cancer. Curr Mol Med. 2006;6:45–654.

    Article  PubMed  CAS  Google Scholar 

  4. Sharp S, Workman P. Inhibitors of the HSP90 molecular chaperone: current status. Adv Cancer Res. 2006;95:323–48.

    Article  PubMed  CAS  Google Scholar 

  5. Tsutsumi S, Namba T, Tanaka KI, Arai Y, Ishihara T, Aburaya M, Mima S, Hoshino T, Mizushima T. Celecoxib upregulates endoplasmic reticulum chaperones that inhibit celecoxib induced apoptosis in human gastric cells. Oncogene. 2006;25:1018–29.

    Article  PubMed  CAS  Google Scholar 

  6. Alloza I, Baxter A, Chen Q, Matthiesen R, Vandenbroeck K. Celecoxib inhibits interleukin-12 alphabeta and beta2 folding and secretion by a novel COX2-independent mechanism involving chaperones of the endoplasmic reticulum. Mol Pharmacol. 2006;69:1579–87.

    Article  PubMed  CAS  Google Scholar 

  7. Kim KW, Moretti L, Mitchell LR, Jung DK, Lu B. Endoplasmic reticulum stress mediates radiation-induced autophagy by perk-eIF2alpha in caspase-3/7-deficient cells. Oncogene. 2010;29:3241–51.

    Article  PubMed  CAS  Google Scholar 

  8. Harding HP, Calfon M, Urano F, Novoa I, Ron D. Transcriptional and translational control in the mammalian unfolded protein response. Annu Rev Cell Dev Biol. 2002;18:575–99.

    Article  PubMed  CAS  Google Scholar 

  9. Sidrauski C, Chapman R, Walter P. The unfolded protein response: an intracellular signaling pathway with many surprising features. Trends Cell Biol. 1998;8:245–9.

    Article  PubMed  CAS  Google Scholar 

  10. Hubbard MJ, McHugh NJ, Carne DL. Isolation of ERp29, a novel endoplasmic reticulum protein, from rat enamel cells evidence for a unique role in secretory protein synthesis. Eur J Biochem. 2000;267:1945–57.

    Article  PubMed  CAS  Google Scholar 

  11. Mkrtchian S, Baryshev M, Matvijenko O, Sharipo A, Sandalova T, Schneider G, Ingelman-Sundberg M. Oligomerization properties of ERp29, an endoplasmic reticulum stress protein. FEBS Lett. 1998;431:322–6.

    Article  PubMed  CAS  Google Scholar 

  12. Hung YC, Wang PW, Pan TL, Bazylak G, Leu YL. Proteomic screening of antioxidant effects exhibited by radix Salvia miltiorrhiza aqueous extract in cultured rat aortic smooth muscle cells under homocysteine treatment. J Ethnopharmacol. 2009;124:463–74.

    Article  PubMed  CAS  Google Scholar 

  13. Dukes AA, Van Laar VS, Cascio M, Hastings TG. Changes in endoplasmic reticulum stress proteins, aldolase A in cells exposed to dopamine. J Neurochem. 2008;106:333–46.

    Article  PubMed  CAS  Google Scholar 

  14. Zhang B, Wang M, Yang Y, Wang Y, Pang X, Su Y, Wang J, Ai G, Zou Z. ERp29 is a radiation-responsive gene in IEC-6 Cell. Radiat Res. 2008;49:587–96.

    Article  Google Scholar 

  15. Zhang D, Putti TC. Over-expression of ERp29 attenuates doxorubicin-induced cell apoptosis through up-regulation of Hsp27 in breast cancer cells. Exp Cell Res. 2010;316:3522–31.

    Article  PubMed  CAS  Google Scholar 

  16. Konishi H, Matsuzaki H, Tanaka M, Takemura Y, Kuroda S, Ono Y, et al. Activation of protein kinase B (Akt/RAC-protein kinase) by cellular stress and its association with heat shock protein Hsp27. FEBS Lett. 1997;410:493–8.

    Article  PubMed  CAS  Google Scholar 

  17. Bruey JM, Ducasse C, Bonniaud P, Ravagnan L, Susin SA, Diaz-Latoud C, et al. Hsp27 negatively regulates cell death by interacting with cytochrome c. Nat Cell Biol. 2000;2:645–52.

    Article  PubMed  CAS  Google Scholar 

  18. Yang YX, Sun XF, Cheng AL, Zhang GY, Yi H, Sun Y, Hu HD, Hu P, Ye F, Chen ZC, Xiao ZQ. Increased expression of HSP27 linked to vincristine resistance in human gastric cancer cell line. J Cancer Res Clin Oncol. 2009;135:181–9.

    Article  PubMed  CAS  Google Scholar 

  19. Kamada M, So A, Muramaki M, Rocchi P, Beraldi E, Gleave M. Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells. Mol Cancer Ther. 2007;6:299–308.

    Article  PubMed  CAS  Google Scholar 

  20. IV Maliutina, Kabakov AE. Preirradiation heat shock protein induction increases cellular radioresistance. Radiats Biol Radioecol. 2007;47:273–9.

    Google Scholar 

  21. To EW, Chan KC, Leung SF, Chan LY, To KF, Chan AT, Johnson PJ, Lo YM. Rapid clearance of plasma Epstein-Barr virus DNA after surgical treatment of nasopharyngeal carcinoma. Clin Cancer Res. 2003;9:3254–9.

    PubMed  CAS  Google Scholar 

  22. Hara A, Okayasu I. Cyclooxygenase-2 and inducible nitric oxide synthase expression in human astrocytic gliomas: correlation with angiogenesis and prognostic significance. Acta Neuropathol. 2004;108:43–8.

    Article  PubMed  CAS  Google Scholar 

  23. Samali A, Robertson JD, Peterson E, Manero F, van Zeijl L, Paul C, Cotgreave IA, Arrigo AP, Orrenius S. Hsp27 protests mitochondria of thermotolerant cells against apoptotic stimuli. Cell Stress Chaperons. 2001;6:49–58.

    Article  CAS  Google Scholar 

  24. Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12:421–9.

    Article  PubMed  Google Scholar 

  25. Chow E, Payne D, O’Sullivan B, Pintilie M, Liu FF, Waldron J, Warde P, Cummings B. Radiotherapy alone in patients with advanced nasopharyngeal cancer: comparison with an intergroup study. Is combined modality treatment really necessary? Radiother Oncol. 2002;63:269–74.

    Article  PubMed  Google Scholar 

  26. Lee N, Xia P, Quivey JM, Sultanem K, Poon I, Akazawa C, Akazawa P, Weinberg V, Fu KK. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys. 2002;53:12–22.

    Article  PubMed  Google Scholar 

  27. Leung SF, Teo PM, Shiu WW, Tsao SY, Leung TW. Clinical features and management of distant metastases of nasopharyngeal carcinoma. J Otolaryngol. 1991;20:27–9.

    PubMed  CAS  Google Scholar 

  28. Lee AS, Hendershot LM. ER stress and cancer. Cancer Biol Ther. 2006;5:721–2.

    Article  PubMed  CAS  Google Scholar 

  29. Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res. 2007;67:3496–9.

    Article  PubMed  CAS  Google Scholar 

  30. Hubbard MJ. Functional proteomics: the goalposts are moving. Proteomics. 2002;2:1069–78.

    Article  PubMed  CAS  Google Scholar 

  31. Van Anken E, Romijn EP, Maggioni C, Mezghrani A, Sitia R, Braakman I, Heck AJ. Sequential waves of functionally related proteins are expressed when B cells prepare for antibody secretion. Immunity. 2003;18:243–53.

    Article  PubMed  Google Scholar 

  32. Baryshev M, Sargsyan E, Wallin G, Lejnieks A, Furudate S, Hishinuma A, Mkrtchian S. Unfolded protein response is involved in the pathology of human congenital hypothyroid goiter and rat non-goitrous congenital hypothyroidism. J Mol Endocrinol. 2004;32:903–20.

    Article  PubMed  CAS  Google Scholar 

  33. Li D, Sun F, Wang K. Caloric restriction retards age-related changes in rat retina. Biochem Biophys Res Commun. 2003;318:253–8.

    Article  Google Scholar 

  34. Myung JK, Afjehi-Sadat L, Felizardo-Cabatic M, et al. Expressional patterns of chaperones in ten human tumor cell lines. Proteome Sci. 2004;2:8.

    Article  PubMed  Google Scholar 

  35. Cheretis C, Dietrich F, Chatzistamou I, et al. Expression of ERp29, an endoplasmic reticulum secretion factor in basal-cell carcinoma. Am J Dermatopathol. 2006;28:410–2.

    Article  PubMed  Google Scholar 

  36. Shnyder SD, Mangum JE, Hubbard MJ. Triplex Profiling of functionally distinct chaperones (ERp29/PDI/BiP) reveals marked heterogeneity of the endoplasmic reticulum proteome in cancer. J Proteome Res. 2008;7:3364–72.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was funded by grants from the National Natural Science Foundation of China (No. 30872852 and No. 30901664) and the Key program of Natural Science Foundation of Hunan Province (No. 2007KS2003) and Scientific Research Fund of Hunan Provincial Education Department.

Conflict of interest

No declared.

Author information

Authors and Affiliations

  1. Department of Otolaryngology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, Hunan Province, People’s Republic of China

    Lin Qi, Ping Wu, Xin Zhang, Yuanzheng Qiu, Weihong Jiang, Donghai Huang, Yong Liu, Pingqing Tan & Yongquan Tian

Authors
  1. Lin Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ping Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuanzheng Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weihong Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Donghai Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pingqing Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yongquan Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yongquan Tian.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 31 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qi, L., Wu, P., Zhang, X. et al. Inhibiting ERp29 expression enhances radiosensitivity in human nasopharyngeal carcinoma cell lines. Med Oncol 29, 721–728 (2012). https://doi.org/10.1007/s12032-011-9929-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-9929-5

Keywords

Search

Navigation