Epstein-Barr virus upregulates phosphorylated heat shock protein 27 kDa in carcinoma cells using the phosphoinositide 3-kinase/Akt pathway.
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.
Fukagawa
Yuki
Y
Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Nishikawa
Jun
J
Kuramitsu
Yasuhiro
Y
Iwakiri
Dai
D
Takada
Kenzo
K
Imai
Shousuke
S
Satake
Masaaki
M
Okamoto
Takeshi
T
Fujimoto
Masanori
M
Okita
Kiwamu
K
Nakamura
Kazuyuki
K
Sakaida
Isao
I
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000595:Amino Acid Sequence; D000730:Androstadienes / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015967:Gene Expression Regulation, Viral; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D006360:Heat-Shock Proteins; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009025:Morpholines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology; D000077191:Wortmannin
D000730:Androstadienes; D018053:Arsenites; D002867:Chromones; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009025:Morpholines; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D000077191:Wortmannin; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; C057725:HSPB1 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human; C015001:arsenite