Mechanisms of GOLPH3 associated with the progression of gastric cancer: a preliminary study

PLoS One. 2014 Oct 6;9(10):e107362. doi: 10.1371/journal.pone.0107362. eCollection 2014.

Abstract

Study design: To investigate the specific mechanisms by which Golgi phosphoprotein 3 (GOLPH3) affects the progression of gastric cancer and to explore its clinical significance.

Methods: Immunohistochemical analysis was used to evaluate the correlations between GOLPH3, phosphorylated mTOR (p-mTOR), phosphorylated Akt (p-Akt), phosphorylated p70S6 (p-p70S6), phosphorylated 4E-BP1 (p-4E-BP1) and the clinicopathological features of gastric cancer. The mRNA expression levels of GOLPH3, mTOR, Akt, p70S6 and 4E-BP1 in gastric cancer, carcinoma-adjacent and paired normal tissue were analyzed using RT-PCR. Western blotting was used to determine the protein expression of GOLPH3, p-mTOR, p-Akt, p-p70S6 and p-4E-BP1 in tissues.

Results: High expression protein levels of GOLPH3, p-AKT, p-mTOR, p70S6, p-4E-BP1 were positively associated with histological grade (p<0.05), depth of invasion (p<0.05), distant metastasis (p<0.05) and lymph node involvement (p<0.05). Compared with carcinoma-adjacent and paired normal tissues, the mRNA expression levels of GOLPH3, AKT, mTOR, p70S6 and 4EBP1 in gastric cancer tissues were significantly higher. The protein expression levels of GOLPH3, p-AKT, p-mTOR, p-p70S6 and p-4E-BP1 in gastric cancer tissues were also significantly higher than in carcinoma-adjacent and paired normal tissues. A strong positive correlation was observed between GOLPH3, p-mTOR, p-p70S6 and p-4EBP1 expression (r = 0.410, 0.303 and 0.276, respectively, p<0.05), but no significant correlation between the expression of GOLPH3 and p-Akt was observed.

Conclusions: The GOPLH3 expression level is highly correlated with Akt/mTOR signaling in human gastric cancer samples. GOLPH3 combined with Akt/mTOR signaling activation may play an important role in the development, differentiation, invasion and metastasis of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Aged
  • Cell Cycle Proteins
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomal Protein S6 / genetics
  • Ribosomal Protein S6 / metabolism
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription, Genetic

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • GOLPH3 protein, human
  • Membrane Proteins
  • Phosphoproteins
  • RNA, Messenger
  • Ribosomal Protein S6
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Grants and funding

This study was supported by the Research Foundation of Guangxi Health Appropriate Technology and Development Project (Grant number: S201415-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.