PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
 
Br J Cancer. 2001 February; 84(3): 335–339.
PMCID: PMC2363738

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

Abstract

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 http://www.bjcancer.com

Keywords: cyclo-oxygenase-2, p53 gene, mutation, gastric cancer

Full Text

The Full Text of this article is available as a PDF (186K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J. 1998 Sep;12(12):1063–1073. [PubMed]
  • Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP, Meltzer SJ, Wilson KT. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology. 1999 Jun;116(6):1319–1329. [PubMed]
  • Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med. 1994 Aug 15;121(4):241–246. [PubMed]
  • Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature. 1991 Apr 4;350(6317):427–428. [PubMed]
  • Hsi LC, Angerman-Stewart J, Eling TE. Introduction of full-length APC modulates cyclooxygenase-2 expression in HT-29 human colorectal carcinoma cells at the translational level. Carcinogenesis. 1999 Nov;20(11):2045–2049. [PubMed]
  • Imazeki F, Omata M, Nose H, Ohto M, Isono K. p53 gene mutations in gastric and esophageal cancers. Gastroenterology. 1992 Sep;103(3):892–896. [PubMed]
  • Ko LJ, Prives C. p53: puzzle and paradigm. Genes Dev. 1996 May 1;10(9):1054–1072. [PubMed]
  • Mack DH, Vartikar J, Pipas JM, Laimins LA. Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53. Nature. 1993 May 20;363(6426):281–283. [PubMed]
  • Matozaki T, Sakamoto C, Matsuda K, Suzuki T, Konda Y, Nakano O, Wada K, Uchida T, Nishisaki H, Nagao M, et al. Missense mutations and a deletion of the p53 gene in human gastric cancer. Biochem Biophys Res Commun. 1992 Jan 15;182(1):215–223. [PubMed]
  • Murata H, Kawano S, Tsuji S, Tsuji M, Sawaoka H, Kimura Y, Shiozaki H, Hori M. Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol. 1999 Feb;94(2):451–455. [PubMed]
  • Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030–3034. [PubMed]
  • Okamoto A, Sameshima Y, Yokoyama S, Terashima Y, Sugimura T, Terada M, Yokota J. Frequent allelic losses and mutations of the p53 gene in human ovarian cancer. Cancer Res. 1991 Oct 1;51(19):5171–5176. [PubMed]
  • Renault B, van den Broek M, Fodde R, Wijnen J, Pellegata NS, Amadori D, Khan PM, Ranzani GN. Base transitions are the most frequent genetic changes at P53 in gastric cancer. Cancer Res. 1993 Jun 1;53(11):2614–2617. [PubMed]
  • Ristimäki A, Honkanen N, Jänkälä H, Sipponen P, Härkönen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res. 1997 Apr 1;57(7):1276–1280. [PubMed]
  • Seto E, Usheva A, Zambetti GP, Momand J, Horikoshi N, Weinmann R, Levine AJ, Shenk T. Wild-type p53 binds to the TATA-binding protein and represses transcription. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028–12032. [PubMed]
  • Sheehan KM, Sheahan K, O'Donoghue DP, MacSweeney F, Conroy RM, Fitzgerald DJ, Murray FE. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA. 1999 Oct 6;282(13):1254–1257. [PubMed]
  • Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A, Dannenberg AJ. Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem. 1999 Apr 16;274(16):10911–10915. [PubMed]
  • Sung JJ, Leung WK, Go MY, To KF, Cheng AS, Ng EK, Chan FK. Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am J Pathol. 2000 Sep;157(3):729–735. [PubMed]
  • Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (Part II). J Natl Cancer Inst. 1998 Nov 4;90(21):1609–1620. [PubMed]
  • Thun MJ, Namboodiri MM, Heath CW., Jr Aspirin use and reduced risk of fatal colon cancer. N Engl J Med. 1991 Dec 5;325(23):1593–1596. [PubMed]
  • Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3336–3340. [PubMed]
  • Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998 May 29;93(5):705–716. [PubMed]
  • Uchino S, Noguchi M, Ochiai A, Saito T, Kobayashi M, Hirohashi S. p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer. Int J Cancer. 1993 Jul 9;54(5):759–764. [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK