The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines.
Pancreatic cancer cells are usually resistant to apoptosis mediated by intrinsic or extrinsic factors. BAG-3 (Bis, CAIR), which was identified as a BAG-1-related protein, is a novel modulator of cellular anti-apoptotic activity that functions through its interaction with Bcl-2. In this study we analyzed BAG-3 expression in human pancreatic cancer tissues and cell lines. BAG-3 mRNA was expressed at moderate to high levels in all pancreatic cancer samples, but at low levels in normal pancreas tissues. In situ hybridization and immunohistochemistry analysis revealed that BAG-3 was present in the cancer cells within the pancreatic tumor mass. When BAG-3 mRNA was analyzed in other gastrointestinal cancers (hepatocellular carcinoma; esophageal, stomach and colon cancer), no difference was found from their corresponding normal controls. In pancreatic cancer cells, BAG-3 mRNA expression levels were strongly induced after heat stress, but not in response to members of the tumor necrosis factor (TNF)-alpha family (TNF-alpha, TRAIL, FasL). These findings indicate that in pancreatic cancer, in contrast to other gastrointestinal malignancies, increased levels of BAG-3 might function to block apoptosis. This characteristic of pancreatic cancer might contribute to its more aggressive growth behavior and poor responsiveness to treatment in vivo.
Liao
Q
Q
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Ozawa
F
F
Friess
H
H
Zimmermann
A
A
Takayama
S
S
Reed
J C
JC
Kleeff
J
J
Büchler
M W
MW
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D002352:Carrier Proteins; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha