Phosphorylation status of Akt and caspase-9 in gastric and colorectal carcinomas

Int J Clin Exp Pathol. 2014 May 15;7(6):3312-7. eCollection 2014.


The serine/threonine protein kinase B/Akt plays a central role in the coordination of multiple signal transduction processes involved in transcriptional regulation, cell survival, and apoptosis. Activation of Akt kinase is a prognostic factor in several types of cancers; however, its role in gastrointestinal cancers is not fully understood. Caspase-9 is an Akt substrate that belongs to the caspase family of proteases, which function as initiators of the mitochondrial apoptotic pathway. Little is known about the role of caspase-9 phosphorylation, which downregulates the apoptotic activity of the enzyme. In this study, we investigated the expression of phosphorylated (p)-Akt and phosphorylated (p)-caspase-9 in gastric and colorectal carcinoma and the relationship between p-Akt and p-caspase-9 expression and clinicopathological parameters of gastric and colorectal cancer patients. In total, 75 samples of advanced gastric adenocarcinoma (37 well-to-moderately differentiated and 38 poorly differentiated) and 76 samples of advanced colorectal adenocarcinoma (69 well-to-moderately differentiated and 7 poorly differentiated) were analyzed for p-Akt and p-caspase-9 expression by immunohistochemistry. Our results reveal a correlation between p-Akt and p-caspase-9 expression in gastric and colorectal cancers. Levels of p-caspase-9 were significantly higher in colorectal cancer than in gastric cancer, indicating tumor-specific regulation. Although the biological role of p-Akt/p-caspase-9 signaling remains unclear, we suggest that phosphorylation of caspase-9 may be a useful tool to assess the state of gastrointestinal cancer and the effects of anti-cancer therapy.

Keywords: Phosphorylated Akt; apoptosis; cell death pathway; gastrointestinal carcinoma; phosphorylated caspase-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Aged
  • Caspase 9 / metabolism*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*


  • Proto-Oncogene Proteins c-akt
  • Caspase 9