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Expression of the molecular chaperone αB-crystallin in infiltrating ductal breast carcinomas and the significance thereof: an immunohistochemical and proteomics-based strategy

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Tumor Biology

Abstract

This study aims to evaluate αB-crystallin expression in infiltrating ductal breast carcinomas (IDCAs), as well as, its prognostic significance. Using a two-dimensional electrophoresis matrix-assisted laser desorption/ionisation-time of flight mass spectrometry investigation coupled to an immunohistochemical approach, we have assessed the expression of αB-crystallin in IDCAs, as well as, in other types of breast tumors (invasive lobular carcinomas, medullary carcinomas, and in situ ductal carcinomas). Correlation between αB-crystallin expression and clinicopathological parameters of breast cancer has also been investigated. Proteomic analyses revealed an increased expression of αB-crystallin in IDCA tumors compared to adjacent nontumor tissues. Overexpression of this molecular chaperone was further confirmed in 51 tumor specimens. Statistical analyses revealed, however, no significant correlations between αB-crystallin expression and clinicopathological parameters of the disease (tumor stage, patient age, hormone receptors, SBR grade, and lymph node metastases). This study demonstrates the upregulation of αB-crystallin in IDCA tissues which may highlight its possible involvement in breast cancer development. Our findings do not, however, support the involvement of this molecular chaperone in the progression of this disease.

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References

  1. Hondermarck H, Vercoutter-Edouart AS, Révillion F, Lemoine J, El-Yazidi-Belkoura I, Nurcombe V, et al. Proteomics of breast cancer for marker discovery and signal pathway profiling. Proteomics. 2001;1:1216–32.

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics. CA Cancer J Clin. 2008;58:71–96.

    Article  PubMed  Google Scholar 

  3. Hill C, Doyon F. Frequency of cancer in France: 2004 update. Bull Cancer. 2004;91:9–14.

    Article  PubMed  Google Scholar 

  4. Hondermarck H. Breast cancer: when proteomics challenges biological complexity. Mol Cell Proteomics. 2003;2:281–91.

    PubMed  CAS  Google Scholar 

  5. Baskın Y, Yiğitbaşı T. Clinical proteomics of breast cancer. Curr Genomics. 2010;11:528–36.

    Article  PubMed  Google Scholar 

  6. Jotwani AC, Gralow JR. Early detection of breast cancer: new biomarker tests on the horizon? Mol Diagn Ther. 2009;13:349–57.

    Article  PubMed  CAS  Google Scholar 

  7. Somiari RI, Sullivan A, Russell S, Somiari S, Hu H, Jordan R, et al. High throughput proteomic analysis of human infiltrating ductal carcinoma of the breast. Proteomics. 2003;3:1863–73.

    Article  PubMed  CAS  Google Scholar 

  8. Othman MI, Majid MI, Singh M, Man CN, Lay-Harn G. Isolation, identification and quantification of differentially expressed proteins from cancerous and normal breast tissues. Ann Clin Biochem. 2008;45:299–306.

    Article  PubMed  CAS  Google Scholar 

  9. Lee HH, Lim CA, Cheong YT, Singh M, Gam LH. Comparison of protein expression profiles of different stages of lymph nodes metastasis in breast cancer. Int J Biol Sci. 2012;8:353–62.

    Article  PubMed  CAS  Google Scholar 

  10. O’Neill PA, Shaaban AM, West CR, Dodson A, Jarvis C, Moore P, et al. Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27. Br J Cancer. 2004;90:182–8.

    Article  PubMed  Google Scholar 

  11. Diehl MC, Idowu MO, Kimmelshue K, York TP, Elmore LW, Holt SE. Elevated expression of nuclear Hsp90 in invasive breast tumors. Cancer Biol Ther. 2009;8:1952–61.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang D, Tai LK, Wong LL, Chiu LL, Sethi SK, Koay ES. Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer. Mol Cell Proteomics. 2005;4:1686–96.

    Article  PubMed  CAS  Google Scholar 

  13. Ramagli LS, Rodriguez LV. Quantification of microgram amounts of proteins in two-dimensional polyacrylamide gel electrophoresis sample buffer. Electrophoresis. 1985;6:559–63.

    Article  CAS  Google Scholar 

  14. O’Farrell PZ, Goodman HM, O’Farrell PH. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977;12:1133–41.

    Article  PubMed  Google Scholar 

  15. Gruvberger-Saal SK, Parsons R. Is the small heat shock protein alphaB-crystallin an oncogene? J Clin Invest. 2006;116:30–2.

    Article  PubMed  CAS  Google Scholar 

  16. Adhikari AS, Singh BN, Rao KS, Rao CM. αB-crystallin, a small heat shock protein, modulates NF-κB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-α induced cytotoxicity. Biochim Biophys Acta. 2011;1813:1532–42.

    Article  PubMed  CAS  Google Scholar 

  17. Mineva I, Gartner W, Hauser P, Kainz A, Löffler M, Wolf G, et al. Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing. Cell Stress Chaperones. 2005;10:171–84.

    Article  PubMed  CAS  Google Scholar 

  18. Chen J, He QY, Yuen AP, Chiu JF. Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis. Proteomics. 2004;4:2465–75.

    Article  PubMed  CAS  Google Scholar 

  19. Ho PY, Chueh SC, Chiou SH, Wang SM, Lin WC, Lee IL, et al. αB-Crystallin in clear cell renal cell carcinoma: tumor progression and prognostic significance. Urol Oncol. 2012. doi:10.1016/j.urolonc.2012.01.015.

  20. Pinder SE, Balsitis M, Ellis IO, Landon M, Mayer RJ, Lowe J. The expression of alpha B-crystallin in epithelial tumours: a useful tumour marker? J Pathol. 1994;174:209–15.

    Article  PubMed  CAS  Google Scholar 

  21. Chan SK, Lui PC, Tan PH, Yamaguchi R, Moriya T, Yu AM, et al. Increased alpha-B-crystallin expression in mammary metaplastic carcinomas. Histopathology. 2011;59:247–55.

    PubMed  Google Scholar 

  22. Moyano JV, Evans JR, Chen F, Lu M, Werner ME, Yehiely F, et al. AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer. J Clin Invest. 2006;116:261–70.

    Article  PubMed  CAS  Google Scholar 

  23. Kamradt MC, Chen F, Cryns VL. The small heat shock protein alpha B-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. J Biol Chem. 2001;276:16059–63.

    Article  PubMed  CAS  Google Scholar 

  24. Watanabe G, Kato S, Nakata H, Ishida T, Ohuchi N, Ishioka C. alphaB-crystallin: a novel p53-target gene required for p53-dependent apoptosis. Cancer Sci. 2009;100:2368–75.

    Article  PubMed  CAS  Google Scholar 

  25. He QY, Chen J, Kung HF, Yuen AP, Chiu JF. Identification of tumor-associated proteins in oral tongue squamous cell carcinoma by proteomics. Proteomics. 2004;4:271–8.

    Article  PubMed  CAS  Google Scholar 

  26. Jäättelä M. Escaping cell death: survival proteins in cancer. Exp Cell Res. 1999;248:30–43.

    Article  PubMed  Google Scholar 

  27. Verschuure P, Croes Y, van den IJssel PR, Quinlan RA, de Jong WW, Boelens WC. Translocation of small heat shock proteins to the actin cytoskeleton upon proteasomal inhibition. J Mol Cell Cardiol. 2002;34:117–28.

    Article  PubMed  CAS  Google Scholar 

  28. Shen J, Person MD, Zhu J, Abbruzzese JL, Li D. Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. Cancer Res. 2004;64:9018–26.

    Article  PubMed  CAS  Google Scholar 

  29. Kageyama S, Isono T, Iwaki H, Wakabayashi Y, Okada Y, Kontani K, et al. Identification by proteomic analysis of calreticulin as a marker for bladder cancer and evaluation of the diagnostic accuracy of its detection in urine. Clin Chem. 2004;50:857–66.

    Article  PubMed  CAS  Google Scholar 

  30. Ivanov O, Chen F, Wiley EL, Keswani A, Diaz LK, Memmel HC, et al. alphaB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat. 2008;111:411–7.

    Article  PubMed  CAS  Google Scholar 

  31. Dejeans N, Glorieux C, Guenin S, Beck R, Sid B, Rousseau R, et al. Overexpression of GRP94 in breast cancer cells resistant to oxidative stress promotes high levels of cancer cell proliferation and migration: implications for tumor recurrence. Free Radic Biol Med. 2012;52:993–1002.

    Article  PubMed  CAS  Google Scholar 

  32. Li DQ, Wang L, Fei F, Hou YF, Luo JM, Wei-Chen, et al. Identification of breast cancer metastasis-associated proteins in an isogenic tumor metastasis model using two-dimensional gel electrophoresis and liquid chromatography-ion trap-mass spectrometry. Proteomics. 2006;6:3352–68.

    Article  PubMed  CAS  Google Scholar 

  33. Gibert B, Eckel B, Gonin V, Goldschneider D, Fombonne J, Deux B, et al. Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo. Br J Cancer. 2012;107:63–70.

    Article  PubMed  CAS  Google Scholar 

  34. Martins I, Kepp O, Galluzzi L, Senovilla L, Schlemmer F, Adjemian S, et al. Surface-exposed calreticulin in the interaction between dying cells and phagocytes. Ann N Y Acad Sci. 2010;1209:77–82.

    Article  PubMed  CAS  Google Scholar 

  35. Liang S, Singh M, Gam LH. The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to ethnicity of the patients; Chinese, Malay and Indian. Dis Markers. 2010;28:149–65.

    PubMed  CAS  Google Scholar 

  36. Chahed K, Kabbage M, Ehret-Sabatier L, Lemaitre-Guillier C, Remadi S, Hoebeke J, et al. Expression of fibrinogen E-fragment and fibrin E-fragment is inhibited in the human infiltrating ductal carcinoma of the breast: the two-dimensional electrophoresis and MALDI-TOF-mass spectrometry analyses. Int J Oncol. 2005;27:1425–31.

    PubMed  CAS  Google Scholar 

  37. Kiang JG, Tsokos GC. Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol Ther. 1998;80:183–201.

    Article  PubMed  CAS  Google Scholar 

  38. Simon S, Fontaine JM, Martin JL, Sun X, Hoppe AD, Welsh MJ, et al. Myopathy-associated alphaB-crystallin mutants: abnormal phosphorylation, intracellular location, and interactions with other small heat shock proteins. J Biol Chem. 2007;282:34276–87.

    Article  PubMed  CAS  Google Scholar 

  39. van Rijk AE, Stege GJ, Bennink EJ, May A, Bloemendal H. Nuclear staining for the small heat shock protein alphaB-crystallin colocalizes with splicing factor SC35. Eur J Cell Biol. 2003;82:361–8.

    Article  PubMed  Google Scholar 

  40. Cherneva R, Petrov D, Georgiev O, Slavova Y, Toncheva D, Stamenova M, et al. Expression profile of the small heat-shock protein alpha-B-crystallin in operated-on non-small-cell lung cancer patients: clinical implication. Eur J Cardiothorac Surg. 2010;37:44–50.

    Article  PubMed  Google Scholar 

  41. Wulfkuhle JD, Sgroi DC, Krutzsch H, McLean K, McGarvey K, Knowlton M, et al. Proteomics of human breast ductal carcinoma in situ. Cancer Res. 2002;62:6740–9.

    PubMed  CAS  Google Scholar 

  42. Boslooper K, King-Yin Lam A, Gao J, Weinstein S, Johnson N. The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma. Pathology. 2008;40:500–4.

    Article  PubMed  CAS  Google Scholar 

  43. Goplen D, Bougnaud S, Rajcevic U, Bøe SO, Skaftnesmo KO, Voges J, et al. αB-crystallin is elevated in highly infiltrative apoptosis-resistant glioblastoma cells. Am J Pathol. 2010;177:1618–28.

    Article  PubMed  CAS  Google Scholar 

  44. Evans JR, Bosman JD, Brown-Endres L, Yehiely F, Cryns VL. Induction of the small heat shock protein alphaB-crystallin by genotoxic stress is mediated by p53 and p73. Breast Cancer Res Treat. 2010;122:159–68.

    Article  PubMed  CAS  Google Scholar 

  45. Sablina AA, Budanov AV, Ilyinskaya GV, Agapova LS, Kravchenko JE, Chumakov PM. The antioxidant function of the p53 tumor suppressor. Nat Med. 2005;11:1306–13.

    Article  PubMed  CAS  Google Scholar 

  46. Kim HS, Lee Y, Lim YA, Kang HJ, Kim LS. αB-crystallin is a novel oncoprotein associated with poor prognosis in breast cancer. J Breast Cancer. 2011;14:14–9.

    Article  PubMed  Google Scholar 

  47. Huang Z, Cheng Y, Chiu PM, Cheung FM, Nicholls JM, Kwong DL, et al. Tumor suppressor alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties. Oncogene. 2011. doi:10.1038/onc.2011.529.

  48. Von Mensdorff-Pouilly S, Petrakou E, Kenemans P, van Uffelen K, Verstraeten AA, Snijdewint FG, et al. Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and n-acetylg alactosamine (GalNA c) peptides. Int J Cancer. 2000;86:702–12.

    Article  Google Scholar 

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Acknowledgments

This work was supported by le Ministère de l’Enseignement Supérieur et de la Recherche Scientifique, le Ministère de la Santé Publique de la République Tunisienne and by the Centre National de Recherche Scientifique (Strasbourg, France).

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Correspondence to Karim Chahed.

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Kabbage, M., Trimeche, M., ben Nasr, H. et al. Expression of the molecular chaperone αB-crystallin in infiltrating ductal breast carcinomas and the significance thereof: an immunohistochemical and proteomics-based strategy. Tumor Biol. 33, 2279–2288 (2012). https://doi.org/10.1007/s13277-012-0490-4

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  • DOI: https://doi.org/10.1007/s13277-012-0490-4

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