title: Role of increased basal expression of heat shock protein 72 in colonic epithelial c2BBE adenocarcinoma cells.
abstract: Although the expression of heat shock proteins (hsps) can be induced by a variety of stressful stimuli, certain neoplasms, including human intestinal T84, HT-29, and Caco2 adenocarcinoma cell lines, express constitutively high levels even under nonstress conditions. In this study, we examine the functional significance of increased hsp72 in spontaneously differentiating Caco2bbe (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 more 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 reduction of hsp72 did not alter activation of IkappaB. In contrast, mitochondrial cytochrome c release and activation of caspase 9 were significantly delayed in hsp72 antisense cells stimulated either with TNF or monochloramine. In conclusion, high endogenous expression of hsp72 by intestinal adenocarcinoma cells appears to confer selective survival advantage but does not affect their growth and differentiation.
authors.affiliation: The Martin Boyer Laboratories, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. mmusch@medicine.bsd.uchicago.edu
authors.forename: M W
authors.initials: MW
authors.lastname: Musch
authors.forename: B
authors.initials: B
authors.lastname: Kaplan
authors.forename: E B
authors.initials: EB
authors.lastname: Chang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed / Q000166:cytology / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002700:Chloramines / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003574:Cytochrome c Group / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002700:Chloramines; D003574:Cytochrome c Group; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D020672:I-kappa B Proteins; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases; C030816:chloramine