Skip to main content
SpringerLink
Log in

Cyclooxygenase-2 expression in human thyroid disease

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Objectives: Cyclooxygenase (COX)-2, which is the inducible form of the COX enzyme for prostaglandin synthesis and a key mediator of epithelial cell growth, has been shown to be up-regulated in gastrointestinal cancers. Additionally, regular intake of other non-steroidal anti-inflammatory drugs (NSAID) is known to decrease the incidence of these cancers. Therefore, the goals of the present study were to determine the possible involvement of COX-2 in human thyroid diseases. Methods: We used immunohistochemical staining and Western blot analysis to characterize the expression of COX-2 proteins in thyroid tissues from 64 patients with thyroiditis, benign tumors, and malignant tumors with or without metastasis. Immunoreactivity scores were calculated by multiplication of the determined grades. Results: COX-2 proteins were not expressed in normal thyroid tissues. However, each type of tumor tissue showed intense bands of COX-2 protein expression in Western blot analyses, and the immunoreactivity scores were 7.67±1.17 (SD) for thyroiditis, 7.87±0.9 for benign tumors, 7.53±1.53 for follicular cancer, 7.63±1.11 for papillary cancer without metastasis, and 7.17±1.55 for papillary cancer with metastasis. No significant differences were found in the levels of COX-2 expression between different tumor tissue types. Conclusion: No significant correlations were observed between clinical and/or pathological characteristics of thyroid tumors and the intensity of COX-2 protein expression. In addition, we found no difference in COX-2 protein expression between thyroiditis and thyroid tumors. Thus, up-regulation of COX-2 protein synthesis in human thyroid diseases does not appear to be of clinical significance.

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

Similar content being viewed by others

References

  1. Piazza GA, Rahm AL, Krutzsch M, et al. Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res 1995, 55: 3110–6.

    PubMed  CAS  Google Scholar 

  2. Shiff SJ, Koutsos MI, Qiao L, Rigas B. Nonsteroidal anti-inflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: effects on cell cycle and apoptosis. Exp Cell Res 1996, 222: 179–88.

    Article  PubMed  CAS  Google Scholar 

  3. Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. New Engl J Med 1991, 325: 1593–6.

    Article  PubMed  CAS  Google Scholar 

  4. DeWitt DL. Prostaglandin endoperoxide synthase: Regulation of enzyme expression. Biochim Biophys Acta 1991, 1083: 121–34.

    Article  PubMed  CAS  Google Scholar 

  5. O’Neill G, Ford-Hutchinson AW. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett 1993, 330: 156–60.

    PubMed  Google Scholar 

  6. Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 1996, 270: 393–400.

    Google Scholar 

  7. Kargman SL, O’Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 1995, 55: 2556–9.

    PubMed  CAS  Google Scholar 

  8. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase-2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994, 107: 1183–8.

    PubMed  CAS  Google Scholar 

  9. DuBois RN, Radhika A, Reddy BS, Entingh AJ. Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. Gastroenterology 1996, 110: 1259–62.

    Article  PubMed  CAS  Google Scholar 

  10. Uefuji K, Ichikura T, Mochizuki H. Expression of cyclooxygenase-2 in human gastric adenomas and adenocarcinomas. J Surg Oncol 2001, 76: 26–30.

    Article  PubMed  CAS  Google Scholar 

  11. Ristimäki A, Honkanen N, Jänkälä H, Sipponen P, Härkönen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 1997, 57: 1276–80.

    PubMed  Google Scholar 

  12. Waddell WR, Loughry RW. Sulindac for polyposis of the colon. J Surg Oncol 1983, 24: 83–7.

    Article  PubMed  CAS  Google Scholar 

  13. Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from Melbourne Colorectal Cancer Study. Cancer Res 1998, 48: 4399–404.

    Google Scholar 

  14. Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Eng J Med 1991, 325: 1593–6.

    Article  CAS  Google Scholar 

  15. Rosenberg L, Palmer JR, Zauner AG, Warshauer ME, Stolley PD, Shapiro S. A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of the large-bowel cancer. J Natl Cancer Inst 1991, 83: 355–8.

    Article  PubMed  CAS  Google Scholar 

  16. Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW Jr. Aspirin use and risk of fatal cancer. Cancer Res 1993, 53: 1322–7.

    PubMed  CAS  Google Scholar 

  17. Funkhouser EM, Sharp GB. Aspirin and reduced risk of esophageal carcinoma. Cancer 1995, 76: 1116–9.

    Article  PubMed  CAS  Google Scholar 

  18. Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxidase H synthesis (cyclooxygenase)-1 and 2. J Biol Chem 1996, 271: 33157–60.

    Article  PubMed  CAS  Google Scholar 

  19. Herschman HR. Prostaglandin synthase 2. Biochim Biophys Acta 1996, 1299: 125–40.

    Article  PubMed  Google Scholar 

  20. Soh EY, Eigelberger MS, Kim KJ, et al. Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo. Surgery 2000, 128: 1059–65.

    Article  PubMed  CAS  Google Scholar 

  21. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998, 93: 705–16.

    Article  PubMed  CAS  Google Scholar 

  22. Soh EY, Duh QY, Sobhi SA, et al. Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid. J Clin Endocrinol Metab 1997, 82: 3741–7.

    PubMed  CAS  Google Scholar 

  23. Sheng H, Williams CS, Shao J, Liang P, DuBois RN, Beauchamp RD. Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts and the role of mitogen-activated protein kinase pathway. J Biol Chem 1998, 273: 22120–7.

    Article  PubMed  CAS  Google Scholar 

  24. Uefuji K, Ichikura T, Mochizuki H. Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer. Clinical Cancer Res 2000, 6: 135–8.

    CAS  Google Scholar 

  25. Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 1997, 94: 3336–40.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in ApcΔ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996, 87: 803–9.

    Article  PubMed  CAS  Google Scholar 

  27. Williams CS, Smalley W, DuBois RN. Aspirin use and potential mechanisms forcolorectal cancer prevention. J Clin Invest 1997, 100: 1325–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthease and cyclooxygenase-2 n Barrett’s esophagus and associated adenocarcinomas. Cancer Res 1998, 58: 2929–34.

    PubMed  CAS  Google Scholar 

  29. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995, 83: 493–501.

    Article  PubMed  CAS  Google Scholar 

  30. To KF, Chan FK, Cheng AS, Lee TL, Ng YP, Sung JJ. Up-regulation of cyclooxygenase-1 and -2 in human gastric ulcer. Aliment Pharmacol Ther 2001, 15: 25–34.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, School of Medicine, Ajou University, San 5, Wonchon-dong, Youngtong-gu, Suwon city, Kyounggi Province, 442-749, South Korea

    K. J. Lee, Y. S. Jung, W. H. Kim, T. I. Yoon & E. Y. Soh MD, PhD

  2. Department of Pathology, School of Medicine, Ajou University, Suwon, South Korea

    H. J. Joo

Authors
  1. K. J. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. S. Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. H. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. I. Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. J. Joo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Y. Soh MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Y. Soh MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, K.J., Jung, Y.S., Kim, W.H. et al. Cyclooxygenase-2 expression in human thyroid disease. J Endocrinol Invest 31, 111–118 (2008). https://doi.org/10.1007/BF03345576

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345576

Key Words

Search

Navigation