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 sp ontaneous self-association of death domains and inappropriate receptor sign aling. In addition, overexpression of SODD suppresses TNF-alpha-induced cel l death. In this report, we demonstrate increased SODD mRNA levels in pancr eatic cancer (n = 30) in comparison to normal control tissues (n = 20, P < 0.01). In situ hybridization analysis revealed SODD expression predominantl y in the cancer cells within the pancreatic tumor mass. In contrast, SODD m RNA levels were not different (P > 0.05) in four other gastrointestinal can cers (liver, esophagus, stomach, colon) compared with the corresponding nor mal tissues. These findings indicate that in contrast to other gastrointest inal malignancies, in pancreatic cancer SODD might block TNF-alpha-mediated apoptosis which may influence the growth of pancreatic cancer cells. (C) 2 000 Academic Press.