The Gene Expression Status of the PI3K/AKT/mTOR Pathway in Gastric Cancer Tissues and Cell Lines

Pathol Oncol Res. 2016 Oct;22(4):797-805. doi: 10.1007/s12253-016-0066-5. Epub 2016 May 7.

Abstract

The PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism and angiogenesis. Emerging evidence has shown that deregulation of this pathway has a role promoting gastric cancer (GC). The aim was to assess the expression of genes involved in this pathway by qPCR in 23 tumor and 23 non-tumor gastric mucosa samples from advanced GC patients, and in AGS, MKN28 and MKN45 gastric cancer cell lines. Results showed a slight overexpression of PIK3CA, PIK3CB, AKT1, MTOR, RPS6KB1, EIF4EBP1 and EIF4E genes, and a slightly decreased PTEN and TSC1 expression. In AGS, MKN28 and MKN45 cells a significant gene overexpression of PIK3CA, PIK3CB, AKT1, MTOR, RPS6KB1 and EIF4E, and a significant repression of PTEN gene expression were observed. Immunoblotting showed that PI3K-β, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E and p-eIF4E proteins were present in cell lines at different levels, confirming activation of this pathway in vitro. This is the first time this extensive panel of 9 genes within PI3K/AKT/mTOR pathway has been studied in GC to clarify the biological role of this pathway in GC and develop new strategies for this malignancy.

Keywords: AGS, MKN28 and MKN45 cell lines; Gastric cancer; PI3K/AKT/mTOR pathway.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Class I Phosphatidylinositol 3-Kinases
  • Gene Expression / genetics*
  • Humans
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinases / genetics*
  • Phosphoproteins / genetics
  • Proto-Oncogene Proteins c-akt / genetics*
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics*
  • TOR Serine-Threonine Kinases / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • MTOR protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human