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S100A8 mediates the activation of P65/HLA-B/S100A8/BCL-2/Caspase-9 (−3) pathway in laryngeal carcinogenesis

  • Articles
  • Medical Genetics
  • Published:
Chinese Science Bulletin

Abstract

S100 calcium binding protein A8 (S100A8), a possible novel member of NF-kappa B signal pathway in laryngeal squamous cell carcinoma (LSCC), interacts with human leukocyte antigen B (HLA-B) which carries an NF-kappa B binding site within the enhancer A. The objective of this study was to explore the molecular mechanism of S100A8 in laryngeal carcinogenesis. RT-PCR, Western blotting and immunohistochemistry staining were applied to evaluate the expression levels of IKKα, P65, REL-B, S100A8, APAF-1 and BCL-2 genes. The signal transduction passway in which S100A8 might participate was explored by RNA interference. Flow cytometry, TUNEL assay and cell invasion in vitro were used to detect the biological behavior of Hep2 cells induced by S100A8 gene. Our results showed that high expression of S100A8 was related to tumorigenesis in LSCC and negatively correlated with the degree of differentiation, indicating that S100A8 gene could inhibit apoptosis and promote metastasis in LSCC. Additionally, the suppression of S100A8 by RNA interference down-regulated BCL-2 but not APAF-1, P65 and IKKα, while, the suppression of P65 could significantly down-regulate the expression of S100A8 gene. In conclusion, S100A8 plays an important role in P65/HLA-B/S100A8/BCL-2/Caspase-9 (−3) pathway in laryngeal carcinoma.

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References

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2007, 57: 43–66

    Article  PubMed  Google Scholar 

  2. Busquets J M, Garcia H A, Trinidad-Pinedo J, et al. Clinicopathologic characteristics of head and neck squamous cell carcinoma in Puerto Ricans. P R Health Sci J, 2003, 22: 259–264

    PubMed  Google Scholar 

  3. Marioni G, Marchese-Ragona R, Cartei G, et al. Current opinion in diagnosis and treatment of laryngeal carcinoma. Cancer Treat Rev, 2006, 32(7): 504–515

    Article  PubMed  Google Scholar 

  4. Kerkhoff C, Klempt M, Sorg C. Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9). Biochim Biophys Acta, 1998, 1448: 200–211

    Article  PubMed  CAS  Google Scholar 

  5. Gebhardt C, Breitenbach U, Tuckermann J P, et al. Calgranulins S100A8 and S100A9 are negatively regulated by glucocorticoids in a c-Fosdependent manner and overexpressed throughout skin carcinogenesis. Oncogene, 2002, 21(27): 4266–4276

    Article  PubMed  CAS  Google Scholar 

  6. MacFarlane A J, Stover P J. Convergence of genetic, nutritional and inflammatory factors in gastrointestinal cancers. Nutr Rev, 2007, 65(12 Pt 2): S157–S166

    Article  PubMed  Google Scholar 

  7. Ishizuka M, Nagata H, Takagi K, et al. Inflammation-based prognostic score is a novel predictor of postoperative outcome in patients with colorectal cancer. Ann Surg, 2007, 246(6): 1047–1051

    PubMed  Google Scholar 

  8. Stathopoulos G T, Sherrill T P, Cheng D S, et al. Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis. Proc Natl Acad Sci USA, 2007, 104(47): 18514–18519

    Article  PubMed  CAS  Google Scholar 

  9. Courtois G. The NF-kappaB signaling pathway in human genetic diseases. Cell Mol Life Sci, 2005, 62(15): 1682–1691

    Article  PubMed  CAS  Google Scholar 

  10. Maeda S, Omata M. Inflammation and cancer: Role of nuclear factor-kappaB activation. Cancer Sci, 2008, 99(5): 836–842

    Article  PubMed  CAS  Google Scholar 

  11. Fu W, Guo Y, Huang D, et al. Novel partners of S100A8 identified in laryngeal cancer cell lines. Zhonghua Yi Xue Yi Chuan Xue Za Zhi (in Chinese), 2007, 24: 266–270

    CAS  Google Scholar 

  12. Gebhardt C, Németh J, Angel P, et al. S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol, 2006, 72(11): 1622–1631

    Article  PubMed  CAS  Google Scholar 

  13. Yao R, Davidson D D, Lopez-Beltran A, et al. The S100 proteins for screening and prognostic grading of bladder cancer. Histol Histopathol, 2007, 22(9): 1025–1032

    PubMed  CAS  Google Scholar 

  14. El-Rifai W, Moskaluk C A, Abdrabbo M K, et al. Gastric cancers overexpress S100A calcium-binding proteins. Cancer Res, 2002, 62(23): 6823–6826

    PubMed  CAS  Google Scholar 

  15. Seth A, Kitching R, Landberg G, et al. Gene expression profiling of ductal carcinomas in situ and invasive breast tumors. Anticancer Res, 2003, 23(3A): 2043–2051

    PubMed  CAS  Google Scholar 

  16. Arai K, Teratani T, Nozawa R, et al. Immunohistochemical investigation of S100A9 expression in pulmonary adenocarcinoma: S100A9 expression is associated with tumor differentiation. Oncol Rep, 2001, 8(3): 591–596

    PubMed  CAS  Google Scholar 

  17. Luo A, Kong J, Hu G, et al. Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene, 2004, 23(6): 1291–1299

    Article  PubMed  CAS  Google Scholar 

  18. Stulik J, Osterreicher J, Koupilova K, et al. The analysis of S100A9 and S100A8 expression in matched sets of macroscopically normal colon mucosa and colorectal carcinoma: the S100A9 and S100A8 positive cells underlie and invade tumor mass. Electrophoresis, 1999, 20(4/5): 1047–1054

    Article  PubMed  CAS  Google Scholar 

  19. Shen J, Person M D, Zhu J, et al. 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(24): 9018–9026

    Article  PubMed  CAS  Google Scholar 

  20. Cross S S, Hamdy F C, Deloulme J C, et al. Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers. Histopathology, 2005, 46(3): 256–269

    Article  PubMed  CAS  Google Scholar 

  21. Carlsson H, Petersson S, Enerback C. Cluster analysis of S100 gene expression and genes correlating to psoriasin (S100A7) expression at different stages of breast cancer development. Int J Oncol, 2005, 27(6): 1473–1481

    PubMed  CAS  Google Scholar 

  22. Hermani A, Hess J, De Servi B, et al. Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer. Clin Cancer Res, 2005, 11(14): 5146–5152

    Article  PubMed  CAS  Google Scholar 

  23. Yui S, Nakatni Y, Mikami M. Calprotectin (S100A8/S100A9), an inflammatory protein complex from neutrophils with a broad apoptosis-inducing activity. Biol Pharm Bull, 2003, 26(6): 753–760

    Article  PubMed  CAS  Google Scholar 

  24. Newton R A, Hogg N. The human S100 protein MRP-14 is a novel activator of thebeta 2 integrin Mac-1 on neutrophils. J Immunol, 1998, 160: 1427–1435.

    PubMed  CAS  Google Scholar 

  25. Kerkhoff C, Eue I, Sorg C. The regulatory role of MRP8 (S100A8) and MRP14 (S100A9) in the transendothelial migration of human leukocytes. Pathobiology, 1999, 67: 230–232

    Article  PubMed  CAS  Google Scholar 

  26. Gebhardt C, Breitenbach U, Tuckermann J P, et al. Calgranulins S100A8 and S100A9 are negatively regulated by glucocorticoids in a c-Fosdependent manner and overexpressed throughout skin carcinogenesis. Oncogene, 2002, 21(27): 4266–4276

    Article  PubMed  CAS  Google Scholar 

  27. Coultas L, Strasser A. The role of the Bcl-2 protein family in cancer. Semin Cancer Biol, 2003, 13: 115–123

    Article  PubMed  CAS  Google Scholar 

  28. Viemann D, Barczyk K, Vogl T, et al. MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and-independent cell death program. Blood, 2007, 109(6): 2453–2460

    Article  PubMed  CAS  Google Scholar 

  29. Ott H W, Lindner H, Sarg B, et al. Calgranulins in cystic fluid and serum from patients with ovarian carcinomas. Cancer Res, 2003, 63: 7507–7514

    PubMed  CAS  Google Scholar 

  30. Gobin S J, Keijsers V, van Zutphen M, et al. The role of enhancer A in the locus-specific transactivation of classical and nonclassical HLA class I genes by nuclear factor kappa B. J Immunol, 1998, 161: 2276–2283

    PubMed  CAS  Google Scholar 

  31. Guo Y, Liu J, Xu Z, et al. HLA-B gene participates in NF-κB signal pathway partly by regulating S100A8 in the laryngeal carcinoma cell line Hep2. Oncol Rep. 2008, 19(6): 1453–1460

    PubMed  CAS  Google Scholar 

  32. Yen T, Harrison C A, Devery J M, et al. Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli. Blood, 1997, 90(12): 4812–4821

    PubMed  CAS  Google Scholar 

  33. Xu K, Geczy C L. IFN-gamma and TNF regulate macrophage expression of the chemotactic S100 protein S100A8. J Immunol, 2000, 164(9): 4916–4923

    PubMed  CAS  Google Scholar 

  34. Klempt M, Melkonyan H, Hofmann H A, et al. Identification of epithelial and myeloid-specific DNA elements regulating MRP14 gene transcription. J Cell Biochem, 1999, 73(1): 49–55

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Genetics, China Medical University, Shenyang, 110001, China

    DaiFa Huang, WeiNeng Fu, Yan Guo & KaiLai Sun

  2. No. 2 Ward of the Officer, General Hospital of Shenyang Military Region, Shenyang, 110015, China

    DaiFa Huang

  3. Department of Otorhinolaryngology, 463 Hospital of PLA, Shenyang, 110042, China

    ZhenMing Xu & XingHe Sun

Authors
  1. DaiFa Huang
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  2. WeiNeng Fu
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  3. Yan Guo
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  4. ZhenMing Xu
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  5. XingHe Sun
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  6. KaiLai Sun
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Correspondence to KaiLai Sun.

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Contributed equally to this work

Supported by National Natural Science Foundation of China (Grant No. 30171008) and National 863 Project of China (Grant No. 2002BA711A08-18)

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Huang, D., Fu, W., Guo, Y. et al. S100A8 mediates the activation of P65/HLA-B/S100A8/BCL-2/Caspase-9 (−3) pathway in laryngeal carcinogenesis. Chin. Sci. Bull. 53, 2017–2024 (2008). https://doi.org/10.1007/s11434-008-0238-0

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  • DOI: https://doi.org/10.1007/s11434-008-0238-0

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