Over-expression of Ephb4 is associated with carcinogenesis of gastric cancer

Dig Dis Sci. 2011 Mar;56(3):698-706. doi: 10.1007/s10620-010-1346-7. Epub 2010 Aug 5.

Abstract

Background: Gastric cancer is one of the most frequently diagnosed malignancies in the world. The gene expression profile and molecular grouping of gastric cancer has been a challenging task due to its inherent complexity and variation among individuals.

Aims: To determine the molecular mechanism associated with gastric carcinogenesis.

Methods: We analyzed the gene expression profiles of 20 cancerous tissues and their tumor-adjacent tissue from patients with gastric cancer by using a 14 K cDNA microarray. The differentially expressed genes and their products were verified by semiquantitative reverse transcription PCR (RT-PCR), western blotting and immunohistochemistry of gastric cancer and normal tissue samples.

Results: A total of 69 genes were found to be differentially regulated in the cancerous tissue. Among them, genes such as CDH17, ETV4, S100A6, S100A11, Ephb4, and KLK10 were confirmed by RT-PCR to be up-regulated, while genes such as NK4 and PPP2R1B were down-regulated. Western blotting and immunohistochemistry indicated that Ephb4 was over-expressed and localized to the cytoplasm of gastric cancer cells. Moreover, Ephb4 protein was observed as being significantly related to tumor size and pN category (p = 0.001 and 0.007, respectively).

Conclusions: These newly identified genes might provide a valuable resource for understanding the molecular mechanism associated with the carcinogenesis of gastric cancer and for finding potential diagnostic markers of gastric cancer.

MeSH terms

  • Adenovirus E1A Proteins / metabolism
  • Adult
  • Aged
  • Cadherins / metabolism
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Cycle Proteins / metabolism
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Kallikreins / metabolism
  • Male
  • Middle Aged
  • Protein Phosphatase 2 / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets
  • Receptor, EphB4 / metabolism*
  • S100 Calcium Binding Protein A6
  • S100 Proteins / metabolism
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • Adenovirus E1A Proteins
  • CDH17 protein, human
  • Cadherins
  • Cell Cycle Proteins
  • ETV4 protein, human
  • HGF protein, human
  • PPP2R1B protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • S100 Calcium Binding Protein A6
  • S100 Proteins
  • S100A6 protein, human
  • S100A11 protein, human
  • Hepatocyte Growth Factor
  • Receptor, EphB4
  • Protein Phosphatase 2
  • KLK10 protein, human
  • Kallikreins