Role of increased basal expression of heat shock protein 72 in colonic epithelial c2BBE adenocarcinoma cells

Although the expression of heat shock proteins (hsps) can be induced by a v ariety of stressful stimuli, certain neoplasms, including human intestinal T84, HT-29, and Caco2 adenocarcinoma cell lines, express constitutively hig h levels even under nonstress conditions. In this study, we examine the fun ctional significance of increased hsp72 in spontaneously differentiating Ca co2bbe (C2) cells. The expression of hsp72 in these cells was specifically inhibited by hsp72 antisense transfection. The loss of hsp72 expression did not affect growth rate, contact inhibition, morphological development, or functional differentiation. In contrast, these cells were significantly mor e sensitive to the injurious effects of oxidants and tumor necrosis factor (TNF) but not doxorubicin. To investigate potential mechanisms of action, a number of steps in the TNF-mediated cell death was measured. Antisense red uction of hsp72 did not alter activation of I kappaB. In contrast, mitochon drial cytochrome c release and activation of caspase 9 were significantly d elayed in hsp72 antisense cells stimulated either with TNF or monochloramin e. In conclusion, high endogenous expression of hsp72 by intestinal adenoca rcinoma cells appears to confer selective survival advantage but does not a ffect theirs growth and differentiation.