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The anti‐apoptotic protein BAG‐3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines
Author(s) -
Liao Quan,
Ozawa Fumiaki,
Friess Helmut,
Zimmermann Arthur,
Takayama Shinichi,
Reed John C.,
Kleeff Jörg,
Büchler Markus W.
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02728-4
Subject(s) - pancreatic cancer , apoptosis , pancreas , cancer , tumor necrosis factor alpha , cancer research , cancer cell , gastrointestinal cancer , immunohistochemistry , ca19 9 , medicine , pancreatic disease , pathology , biology , endocrinology , colorectal cancer , biochemistry
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.