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Quantitative measurement of m-RNA levels to assess expression of cyclooxygenase-II, inducible nitric oxide synthase and 12-lipoxygenase genes in middle ear cholesteatoma

  • Otology
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Abstract

To assess expression of three main inflammatory genes, COX-II, ALOX-12 and i-NOS, quantitatively at transcriptional level in cholesteatoma matrix tissue. Ten patients who have chronic otitis media with primary acquired cholesteatoma were included in this study. Tissue samples obtained from cholesteatoma matrix and external ear canal skin (control tissue). Expression of the targeted genes (COX-II, i-NOS and LOX-12) was assessed using real-time quantitative polymerase chain reaction (RT-PCR) technique. The amount of COX2 mRNA was significantly higher in cholesteatoma matrix at transcriptional level (p = 0.038). There was no statistically significant difference regarding expression of iNOS and LOX12 mRNA levels (p > 0.05). There is a significant overexpression of the mRNA of COX-II in cholesteatoma matrix, which indicates a difference between the normal skin and cholesteatoma matrix at molecular level. COX-II gene overexpression seems to be associated with pathogenesis of cholesteatoma. This molecular change is similar to the molecular abnormalities observed in some benign and malignant neoplasms. Invasive and locally destructive nature of cholesteatoma may be due to COX-II overexpression. Absence of an increase in the gene expressions of i-NOS and LOX-12 in cholesteatoma matrix suggests that these mediators may not be related with the pathogenesis and evolution of cholesteatoma.

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References

  1. Ahn JM, Huang CC, Abramson M (1990) Interleukin-1 causing bone destruction in middle ear cholesteatoma. Otolaryngol Head Neck Surg 103:527–536

    CAS  PubMed  Google Scholar 

  2. Schilling V, Negri B, Bujia J, Schulz P, Kastenbauer E (1992) Possible role of interleukin 1a and interleukin 1b in the pathogenesis of cholesteatoma of middle ear. Am J Otol 13:350–355

    CAS  PubMed  Google Scholar 

  3. Uğar-Cankal D, Ozmeric N (2006) A multifaceted molecule, nitric oxide in oral and periodontal diseases. Clin Chim Acta 366(1–2):90–100

    Article  PubMed  Google Scholar 

  4. Gee J, Lee IL, Jendiroba D, Fischer SM, Grossman HB, Sabichi AL (2006) Selective cyclooxygenase-2 inhibitors inhibit growth and induce apoptosis of bladder cancer. Oncol Rep 15(2):471–477

    CAS  PubMed  Google Scholar 

  5. Skrzypczak-Jankun E, Chorostowska-Wynimko J, Selman SH, Jankun J (2007) Lipoxygenases-a challenging problem in enzyme inhibition and drug development. Curr Enzyme Inhib 3:119–132

    Article  CAS  Google Scholar 

  6. Chole RA (1997) The molecular biology of bone resorption due to chronic otitis media. Ann N Y Acad Sci 830:95–109

    Article  CAS  PubMed  Google Scholar 

  7. Hewett SJ, Bell SC, Hewett JA (2006) Contributions of cyclooxygenase-2 to neuroplasticity and neuropathology of the central nervous system. Pharmacol Ther 112:335–357

    Article  CAS  PubMed  Google Scholar 

  8. Shimuzu T, Radmard O (1990) Arachidonic acid cascade and signal transduction. J Neurochem 55:1–15

    Article  Google Scholar 

  9. Smith WL (1989) The eicosanoids and their biochemical mechanisms of action. Biochem J 259:315–324

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Hall AV, Antoniou H, Wang Y, Cheung AH, Arbus AM, Olson SL, Lu WC, Kau CL, Marsden PA (1994) Structural organization of the human neuronal nitric oxide synthase gene (NOS1). J Biol Chem 269:33082–33090

    CAS  PubMed  Google Scholar 

  11. Jung JY, Pashia ME, Nishimoto SY, Faddis BT, Chole RA (2004) A possible role for nitric oxide in osteoclastogenesis associated with cholesteatoma. Otol Neurotol 25(5):661–668

    Article  PubMed  Google Scholar 

  12. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative Expression Software Tool (REST©) for group wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30(9)

  13. Chole RA, Faddis BT (2002) Evidence for microbial biofilms in cholesteatomas. Arch Otolaryngol Head Neck Surg 128:1129–1133

    Article  PubMed  Google Scholar 

  14. Jung JY, Chole RA (2002) Bone resorption in chronic otitis media: the role of the osteoclast. ORL 64:95–107

    Article  CAS  PubMed  Google Scholar 

  15. Thomsen LL, Lawton FG, Knowles RG, Beesley JE, Riveros-Moreno V, Moncada S (1994) Nitric oxide synthase activity in human gynecological cancer. Cancer Res 54(5):1352–1354

    CAS  PubMed  Google Scholar 

  16. Wilson KT, Fu S, Ramanujam KS, Meltzer SJ (1998) Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett’s esophagus and associated adenocarcinomas. Cancer Res 58(14):2929–2934

    CAS  PubMed  Google Scholar 

  17. Ambs S, Bennett WP, Merriam WG, Ogunfusika MO, Oser SM, Khan MA, Jones RT, Harris CC (1998) Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53. Br J Cancer 78(2):233–239

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Klotz T, Bloch W, Volberg C, Engelmann U, Addicks K (1998) Selective expression of inducible nitric oxide synthase in human prostate carcinoma. Cancer 82(10):1897–1903

    Article  CAS  PubMed  Google Scholar 

  19. Swana HS, Smith SD, Perrotta PL, Saito N, Wheeler MA, Weiss RM (1999) Inducible nitric oxide synthase with transitional cell carcinoma of the bladder. J Urol 161(2):630–634

    CAS  PubMed  Google Scholar 

  20. Hajri A, Metzger E, Vallat F, Coffy S, Flatter E, Evrard S, Marescaux J, Aprahamian M (1998) Role of nitric oxide in pancreatic tumour growth: In vivo and in vitro studies. Br J Cancer 78(7):841–849

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Chen YQ (1994) Endogenous 12(S)-HETE production by tumor cells and its role in metastasis. Cancer Res 54:1574–1579

    CAS  PubMed  Google Scholar 

  22. Gao X (1995) Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer. Urology 46:227–237

    Article  CAS  PubMed  Google Scholar 

  23. Timar J (2000) Expression, subcellular localization and putative function of platelet-type 12-lipoxygenase in human prostate cancer cell line of different metastatic potential. Int J Cancer 87:37–43

    Article  CAS  PubMed  Google Scholar 

  24. Wong BC (2001) 12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells. Carcinogenesis 22:1349–1354

    Article  CAS  PubMed  Google Scholar 

  25. Raso E (2004) Molecular identification, localization and function of platelet-type 12-lipoxygenase in human melanoma progression, under experimental and clinical conditions. Melanoma Res 14:245–250

    Article  CAS  PubMed  Google Scholar 

  26. Bujía J, Holly A, Antolí-Candela F, Tapia MG, Kastenbauer E (1996) Immunobiological peculiarities of cholesteatoma in children: quantification of epithelial proliferation by MIB1. Laryngoscope 106(7):865–868

    Article  PubMed  Google Scholar 

  27. Olszewska E, Wagner M, Bernal-Sprekelsen M, Ebmeyer J, Dazert S, Hildmann H, Sudhoff H (2004) Etiopathogenesis of cholesteatoma. Eur Arch Otorhinolaryngol 261(1):6–24

    Article  PubMed  Google Scholar 

  28. Bujia J, Sudhoff H, Holly A, Hildmann H, Kastenbauer E (1996) Immunohistochemical detection of proliferation cell nuclear antigen in middle ear cholesteatoma. Eur Arch Otorhinolaryngol 253:21–24

    CAS  PubMed  Google Scholar 

  29. Mizutani H, Ohyanagi S, Hayashi T, Groves RW, Suzuki K, Shimizu M (1996) Functional thrombomodulin expression on epithelial skin tumors as a differentiation marker for suprabasal keratinocytes. Br J Dermatol 135:187–193

    Article  CAS  PubMed  Google Scholar 

  30. Sudhoff H, Bujia J, Fisseler-Eckhoff A, Schulz-Flake C, Holly A, Hildmann H (1995) Expression of the cell-cyclerelated antigen (MIB 1) in cholesteatoma and auditory meatal skin. Laryngoscope 105:1227–1231

    Article  CAS  PubMed  Google Scholar 

  31. Albino AP, Kimmelman CP, Parisier SC (1998) Cholesteatoma: a molecular and cellular puzzle. Am J Otol 19(1):7–19

    CAS  PubMed  Google Scholar 

  32. Desloge RB, Carew JF, Finstad CL, Steiner MG, Sassoon J, Levenson MJ, Staiano-Coico L, Parisier SC, Albino AP (1997) DNA analysis of human cholesteatomas. Am J Otol 18:155–159

    CAS  PubMed  Google Scholar 

  33. Bayazit YA, Buyukberber S, Sari I, Camci C, Ozer E, Sevinc A, Karakok M, Kanlikama M, Mumbuc S (2004) Cyclo-oxygenase 2 expression in laryngeal squamous cell carcinoma and its clinical correlates. ORL J Otorhinolaryngol Relat Spec 66(2):65–69

    Article  CAS  PubMed  Google Scholar 

  34. Dannenberg AJ, Altorki NK, Boyle JO (2001) Cyclo-oxygenase 2: A pharmacological target for the prevention of cancer. Lancet Oncol 2:544–551

    Article  CAS  PubMed  Google Scholar 

  35. Kulkarni S, Rader JS, Zhang F (2001) Cyclooxygenase-2 is overexpressed in human cervical cancer. Clin Cancer Res 7:429–434

    CAS  PubMed  Google Scholar 

  36. Fosslien E (2000) Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 30:3–21

    CAS  PubMed  Google Scholar 

  37. Leung WK, To KF, Ng YP et al (2001) Association between cyclo-oxygenase-2 overexpression and missense p53 mutations in gastric cancer. Br J Cancer 84:335–339

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Mestre JR, Subbaramaiah K, Sacks P et al (1997) Retinoids suppress epidermal growth factorinduced transcription of cyclooxygenase-2 in human oral squamous carcinoma cells. Cancer Res 57:2890–2895

    CAS  PubMed  Google Scholar 

  39. (2002) Expression of the p53 and nm23 genes in cholesteatoma. Acta Otolaryngol 122(7):726–729

  40. Bayazít YA, Karakök M, Uçak R, Kanlíkama M (2001) Cycline-dependent kinase inhibitor, p27 (KIP1), is associated with cholesteatoma. Laryngoscope 111(6):1037–1041

    Article  PubMed  Google Scholar 

  41. Morales DS, Penido Nde O, da Silva ID, Stávale JN, Guilherme A, Fukuda Y (2007) Matrix metalloproteinase 2: an important genetic marker for cholesteatomas. Rev Bras Otorrinolaringol 73(1):51–57

    Article  Google Scholar 

  42. Tsujii M, Kawano S, Du Bois RN (1997) Cyclo-oxygenase-2 expression in human colon cancer increases metastatic potential. Proc Natl Acad Sci USA 94:3336–3340

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Correspondence to Tolgahan Çatlı.

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Çatlı, T., Bayazıt, Y., Yılmaz, A. et al. Quantitative measurement of m-RNA levels to assess expression of cyclooxygenase-II, inducible nitric oxide synthase and 12-lipoxygenase genes in middle ear cholesteatoma. Eur Arch Otorhinolaryngol 271, 1471–1475 (2014). https://doi.org/10.1007/s00405-013-2614-x

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  • DOI: https://doi.org/10.1007/s00405-013-2614-x

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