The anti‐apoptotic protein BAG‐3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines

FEBS Letters

Friess, Helmut³  Kleeff, Jörg³  Liao, Quan³  Takayama, Shinichi²  Ozawa, Fumiaki³  Büchler, Markus W.³  Zimmermann, Arthur¹  Reed, John C.² 

[1] Institute of Pathology, University of Bern, Inselspital, Bern, Switzerland;The Burnham Institute, La Jolla, CA, USA;Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, CH-3010 Bern, Switzerland

关键词: BAG-3;    Bis;    CAIR;    Pancreatic cancer;    Gastrointestinal cancer;    Apoptosis;   

DOI  :  10.1016/S0014-5793(01)02728-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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)-α family (TNF-α, 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.

【 授权许可】

Unknown