title: Phosphorylation status of Akt and caspase-9 in gastric and colorectal carcinomas.
abstract: 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.
authors.affiliation: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences Kobe, Japan ; Department of Diagnostic Pathology, Osaka Red Cross Hospital Osaka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sangawa
authors.affiliation: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences Kobe, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shintani
authors.affiliation: Department of Clinical Laboratory, Kuma Hospital Kobe, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamao
authors.affiliation: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences Kobe, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamoshida
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D053453:Caspase 9 / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D053453:Caspase 9
keywords: Phosphorylated Akt; apoptosis; cell death pathway; gastrointestinal carcinoma; phosphorylated caspase-9