ADAM-17 expression is enhanced by FoxM1 and is a poor prognostic sign in gastric carcinoma

J Surg Res. 2017 Dec;220:223-233. doi: 10.1016/j.jss.2017.06.032. Epub 2017 Aug 2.

Abstract

Background: The ADAMs proteases are a multifunctional family of proteins, many of which participate in the pathogenesis of cancers. The expression and regulation of ADAMs has not yet been fully examined in gastric cancer.

Materials and methods: Using reverse transcription-PCR, messenger RNA expression of ADAM-9, ADAM-10, ADAM-11, ADAM-12, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 was detected in gastric cancer. ADAM-10, ADAM-17, ADAM-28, and FoxM1 expression in gastric cancer was detected by Western blot and immunohistochemistry. The correlation between ADAM-17 and FoxM1 was analyzed in vivo and in vitro.

Results: The messenger RNA levels of ADAM-9, ADAM-10, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 were increased in tumor tissues compared with adjacent normal tissue, especially ADAM-10, ADAM-17, and ADAM-28. FoxM1 expression correlated significantly with ADAM-17 expression. FoxM1 regulates ADAM-17 expression in vivo and in vitro, which in turn influences proliferation and tumor growth of gastric cancer cells. Furthermore, Cox regression analysis revealed that FoxM1 and ADAM-17 are independent prognostic factors for patients with gastric cancer.

Conclusions: These results indicate that overexpression of ADAMs may contribute to gastric cancer progression and that ADAM-17 is a downstream target of FoxM1. Overall, the present study highlights the potential for FoxM1 and ADAMs as potential therapeutic targets for patients with gastric carcinoma.

Keywords: ADAMs; FoxM1; Gastric carcinoma; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM17 Protein / metabolism*
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / mortality
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • China / epidemiology
  • Female
  • Forkhead Box Protein M1 / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • ADAM17 Protein
  • ADAM17 protein, human