Enhanced expression of Silencer of death domains (SODD/BAG-4) in pancreatic cancer.
Pancreatic cancers are resistant to TNF-alpha-mediated apoptosis. Silencer of death domains (SODD) binds to TNF-alpha receptor TNFR-1, and prevents spontaneous self-association of death domains and inappropriate receptor signaling. In addition, overexpression of SODD suppresses TNF-alpha-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-alpha-mediated apoptosis which may influence the growth of pancreatic cancer cells.
Ozawa
F
F
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Bern, CH 3010, Switzerland.
Friess
H
H
Zimmermann
A
A
Kleeff
J
J
Büchler
M W
MW
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D016923:Cell Death; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; C116906:BAG4 protein, human; D002352:Carrier Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor