Association between cyclo-oxygenase-2 overexpression and missense p53 mutations in gastric cancer


Wild-type p53 competitively binds to the promoter region of COX-2 in vitro and inhibits its transcription. We examined the association between p53 mutation and COX-2 expression in gastric cancer. COX-2 over-expression was seen in 19 (48.7%) cases. These tumours had more lymph-node metastasis (P = 0.048) and tended to have a poorer survival (P = 0.07). Missense mutations of p53 were detected in 20 (51.3%) patients and had a significantly stronger COX-2 expression than tumours without p53 mutation (P = 0.016). Our results suggest a link between p53 mutation and COX-2 overexpression in gastric cancer. © 2001 Cancer Research Campaign

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  1. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, van de Putte LB and Lipsky PE (1998) Cyclooxygenase in biology and disease. FASEB J 12: 1063–1073

  2. Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP, Meltzer SK and Wilson KT (1999) Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterol 116: 1319–1329

  3. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A and Willett WC (1994) Aspirin use and the risk for colorectal cancer and adenoma in male health professional. Ann Int Med 121: 241–246

  4. Hse IC, Metcalf RA, Sun T, Welsh JA, Wang NJ and Harris CC (1991) Mutational hotspot in the p53 gene in human hepatocellular carcinoma. Nature 350: 427–428

  5. Hsi LC, Angerman-Sterwart J and Eling TE (1999) Introduction of full-length APC modulates cyclooxygenase-2 expression in HT-29 human colorectal carcinoma cells at the translational level. Carcinogenesis 20: 2045–2049

  6. Imazeki F, Omata M, Nose H, Ohto M and Isono K (1992) p53 gene mutations in gastric and esophageal cancers. Gastroenterol 103: 892–896

  7. Ko LJ and Prives C (1996) p53: puzzle and paradigm. Gene & Development 10: 1054–1072

  8. Mack DH, Vartikar J, Pipas JM and Laimins LA (1993) Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53. Nature 363: 281–283

  9. Matozaki T, Sakamoto C, Matsuda K, Suzuki T, Konda Y, Nakano O, Wada K, Uchida T, Nishisaki H, Nagao M and Kasuga M (1992) Missense mutations and a deletion of the p53 gene in human gastric cancer. Biochem Biophy Res Comm 182: 215–223

  10. Murata H, Kawano S, Tsuji S, Tsujii M, Sawaoka H, Kimura Y, Shiozaki H and Hori M (1999) Cyclooxygenase-2 over-expression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol 94: 451–455

  11. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS and Tannenaum SR (1992) DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 89: 3030–3034

  12. Okamoto A, Sameshima Y, Yokoyama S, Terashima Y, Sugimura T, Terada M and Yokota J (1991) Frequent allelic losses and mutations of the p53 gene in human ovarian cancer. Cancer Res 51: 5171–5176

  13. Renault B, van den Broek M, Fodde R, Wijinen J, Pellegata NS, Amadori D, Khan PM and Ranzai GN (1993) Base transitions are the most frequent genetic changes at p53 in gastric cancer. Cancer Res 53: 2614–2617

  14. Ristimaki A, Honkanen N, Jankala H, Sipponen P and Harkonen M (1997) Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 57: 1276–1280

  15. Seto E, Usheva A, Zambetti GP, Momand J, Horikoshi N, Weinmann R, Levine AJ and Shenk T (1992) Wild-type p53 binds to the TATA-binding protein and represses transcription. Proc Natl Acad Sci USA 89: 12028–12032

  16. Sheehan KM, Sheehan K, O’Donoghue DP, MacSweeney F, Conroy RM, Fitzgerald DJ and Murray FE (1999) The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 282: 1254–1257

  17. Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A and Dannenberg AJ (1999) Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem 274: 10911–10915

  18. Sung JJY, Leung WK, Go MYY, To KF, Cheng ASL, Ng EKW and Chan FKL (2000) COX-2 expression in H. pylori -associated premalignant and malignant gastric lesions. Am J Pathol 157: 729–735

  19. Taketo MM (1998) Cyclooxygenase-2 inhibitors in tumorigenesis (Part II). J Natl Cancer Inst 90: 1609–1620

  20. Thun MJ, Namboodiri MM and Health CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325: 1593–1596

  21. Tsujii M, Kawano S and DuBois RN (1997) Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 94: 3336–3340

  22. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M and DuBois RN (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93: 705–716

  23. Uchino S, Noguchi M, Ochiai A, Saito T, Kobayashi M and Hirohashi S (1993) p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer. Int J Cancer 54: 759–764

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Leung, W., To, K., Ng, Y. et al. Association between cyclo-oxygenase-2 overexpression and missense p53 mutations in gastric cancer. Br J Cancer 84, 335–339 (2001).

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  • cyclo-oxygenase-2
  • p53 gene
  • mutation
  • gastric cancer

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