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

Abstract

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.

• Authors: Q Liao, F Ozawa, H Friess, A Zimmermann, S Takayama, J C Reed, J Kleeff, M W Büchler
• Journal: FEBS letters (FEBS Lett) Vol. 503 Issue 2-3 Pg. 151-7 (Aug 17 2001) ISSN: 0014-5793 [Print] England
• PMID: 11513873 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• BAG3 protein, human
• Carrier Proteins
• DNA Primers
• RNA, Messenger
• RNA, Neoplasm
• Tumor Necrosis Factor-alpha

Topics

• Adaptor Proteins, Signal Transducing
• Apoptosis
• Apoptosis Regulatory Proteins
• Base Sequence
• Carrier Proteins (biosynthesis, genetics)
• DNA Primers (genetics)
• Gene Expression (drug effects)
• Hot Temperature
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Pancreas (metabolism)
• Pancreatic Neoplasms (genetics, metabolism, pathology)
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (pharmacology)