4.4 Article

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

Journal

PATHOLOGY & ONCOLOGY RESEARCH
Volume 22, Issue 4, Pages 797-805

Publisher

SPRINGER
DOI: 10.1007/s12253-016-0066-5

Keywords

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

Funding

  1. Chilean National Fund for Scientific and Technological Development (FONDECYT) [1090171, 1130204]
  2. Chilean National Commission for Scientific and Technological Research (CONICYT) through the PhD scholarship [24121456]
  3. Grant CONICYT-FONDAP [15130011]
  4. Universidad de La Frontera

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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-beta, 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.

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