Enhanced Expression of Silencer of Death Domains (SODD/BAG-4) in Pancreatic Cancer

• Published in: Biochemical and biophysical research communications Vol. 271; no. 2; pp. 409 - 413
• Main Authors: Ozawa, Fumiaki, Friess, Helmut, Zimmermann, Arthur, Kleeff, Jörg, Büchler, Markus W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-05-2000
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Aged; apoptosis; BAG-4; BAG-4 protein; Blotting, Northern; Carrier Proteins - biosynthesis; Carrier Proteins - metabolism; Cell Death; Colon - metabolism; Colonic Neoplasms - metabolism; death domain; Esophageal Neoplasms - metabolism; Esophagus - metabolism; Female; gastrointestinal cancer; Humans; In Situ Hybridization; Liver - metabolism; Liver Neoplasms - metabolism; Male; Middle Aged; mRNA; pancreatic cancer; Pancreatic Neoplasms - metabolism; Receptors, Tumor Necrosis Factor - metabolism; RNA, Messenger - metabolism; self-association; Signal Transduction; silencer of death domains; SODD protein; Stomach - metabolism; Stomach Neoplasms - metabolism; Tissue Distribution; TNF-α; TNFR-1; Tumor Cells, Cultured; self-association; pancreatic cancer; TNF-α; gastrointestinal cancer; silencer of death domains; TNFR-1; apoptosis; death domain; mRNA; BAG-4
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.2610

Pancreatic cancers are resistant to TNF-α-mediated apoptosis. Silencer of death domains (SODD) binds to TNF-α receptor TNFR-1, and prevents spontaneous self-association of death domains and inappropriate receptor signaling. In addition, overexpression of SODD suppresses TNF-α-induced cell death. In this report, we demonstrate increased SODD mRNA levels in pancreatic cancer (n = 30) in comparison to normal control tissues (n = 20, P < 0.01). In situ hybridization analysis revealed SODD expression predominantly in the cancer cells within the pancreatic tumor mass. In contrast, SODD mRNA levels were not different (P > 0.05) in four other gastrointestinal cancers (liver, esophagus, stomach, colon) compared with the corresponding normal tissues. These findings indicate that in contrast to other gastrointestinal malignancies, in pancreatic cancer SODD might block TNF-α-mediated apoptosis which may influence the growth of pancreatic cancer cells.