Epstein-Barr virus upregulates phosphorylated heat shock protein 27 kDa in carcinoma cells using the phosphoinositide 3-kinase/Akt pathway.

Abstract

Gastric cancer is the most common cancer in Japan and infection with Epstein-Barr virus (EBV) is responsible for about 10% of gastric cancers worldwide. Although EBV infection may be involved at an early stage of gastric carcinogenesis, the mechanisms underlying its involvement remain unknown. To investigate the role of EBV in gastric carcinogenesis, we performed proteomic analyses of an EBV-infected gastric carcinoma cell line NU-GC-3 (EBV(+)) and its uninfected control (EBV(-)). 2-DE was combined with MS to identify differentially expressed proteins. We found that EBV infection upregulated one of the phosphorylated heat shock protein 27 kDa (HSP27). The phosphorylated HSP27 isoform which increased in EBV(+) cells can be induced by both heat shock and arsenite. The increase of phosphorylated HSP27 in EBV(+) cells was reduced by treatment with the phosphoinositide 3-kinase (PI3K) inhibitors (LY294002 and wortmannin). In addition, we found increased levels of phosphorylated Akt in EBV(+) cells. These findings suggest that EBV infection upregulates the phosphorylation of HSP27 via the PI3K/Akt pathway. Thus, activation of the PI3K/Akt pathway may contribute to the establishment of a malignant phenotype in EBV-infected gastric carcinomas.

• Authors: Yuki Fukagawa, Jun Nishikawa, Yasuhiro Kuramitsu, Dai Iwakiri, Kenzo Takada, Shousuke Imai, Masaaki Satake, Takeshi Okamoto, Masanori Fujimoto, Kiwamu Okita, Kazuyuki Nakamura, Isao Sakaida
• Journal: Electrophoresis (Electrophoresis) Vol. 29 Issue 15 Pg. 3192-200 (Aug 2008) ISSN: 0173-0835 [Print] Germany
• PMID: 18604870 (Publication Type: Journal Article)

Chemical References

• Androstadienes
• Arsenites
• Chromones
• EBV-associated membrane antigen, Epstein-Barr virus
• Epstein-Barr virus encoded RNA 1
• HSP27 Heat-Shock Proteins
• HSPB1 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• Morpholines
• Neoplasm Proteins
• Phosphoinositide-3 Kinase Inhibitors
• Protein Isoforms
• RNA, Viral
• Viral Matrix Proteins
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• arsenite
• Wortmannin

Topics

• Adenocarcinoma (metabolism, pathology, virology)
• Amino Acid Sequence
• Androstadienes (pharmacology)
• Arsenites (pharmacology)
• Cell Line, Tumor
• Cell Transformation, Viral (physiology)
• Chromones (pharmacology)
• Electrophoresis, Gel, Two-Dimensional
• Female
• Gene Expression Regulation, Viral
• HSP27 Heat-Shock Proteins (analysis, biosynthesis, genetics)
• Heat-Shock Proteins
• Herpesvirus 4, Human (physiology)
• Hot Temperature
• Humans
• Male
• Middle Aged
• Molecular Chaperones
• Molecular Sequence Data
• Morpholines (pharmacology)
• Neoplasm Proteins (analysis, biosynthesis, genetics)
• Phosphatidylinositol 3-Kinases (physiology)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation (drug effects)
• Protein Isoforms (analysis, biosynthesis, genetics)
• Protein Processing, Post-Translational (drug effects)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, physiology)
• RNA, Viral (genetics, physiology)
• Signal Transduction (physiology)
• Stomach Neoplasms (metabolism, pathology, virology)
• Up-Regulation
• Viral Matrix Proteins (genetics, physiology)
• Wortmannin