hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions

BMC Gastroenterol. 2012 Jul 6:12:85. doi: 10.1186/1471-230X-12-85.

Abstract

Background: Gastric cancer is a serious public health problem in Northern Brazil and in the world due to its high incidence and mortality. Despite the severity of the disease, more research is needed to better understand the molecular events involved in this intestinal-type gastric carcinogenesis process. Since precancerous lesions precede intestinal-type gastric cancer, here, we evaluated the hTERT, MYC, and TP53 mRNA and protein expression, as well as TP33 copy number, in gastric preneoplastic lesions.

Methods: We evaluated 19 superficial gastritis, 18 atrophic gastritis, and 18 intestinal metaplasia from cancer-free individuals of Northern Brazil. Quantitative reverse transcription PCR was used to analyze the mRNA expression and immunohistochemical methods were used to assess protein immunoreactivity in tissue samples. The number of TP53 gene copies was investigated in gastric diseases by quantitative PCR.

Results: We observed hTERT, MYC, and p53 immunoreactivity only in intestinal metaplasia samples. The immunoreactivity of these proteins was strongly associated with each other. A significantly higher MYC mRNA expression was observed in intestinal metaplasia compared to gastritis samples. Loss of TP53 was also only detected in intestinal metaplasia specimens.

Conclusions: We demonstrated that hTERT, MYC, and TP53 are deregulated in intestinal metaplasia of individuals from Northern Brazil and these alterations may facilitate tumor initiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil
  • Cell Transformation, Neoplastic / metabolism
  • Female
  • Gastritis / genetics
  • Gastritis / metabolism
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Immunohistochemistry
  • Male
  • Metaplasia / genetics
  • Metaplasia / metabolism
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / pathology
  • Proto-Oncogene Proteins c-myc / analysis
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Telomerase / analysis
  • Telomerase / metabolism*
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • TERT protein, human
  • Telomerase