Caspase 7 downregulation as an immunohistochemical marker of colonic carcinoma.
Caspases play a crucial role as apoptotic effectors; their potential implication in tumorigenesis remains to be clarified. We investigated the expression and function of caspases 7, 8, and 9 in colon cancer tissues and cell lines. Immunohistochemistry (IHC) showed downregulation of caspase 7 (22 of 26 cases) and caspase 9 (12 of 26 cases) in colonic cancer samples compared with normal mucosa on the same tissue section. Caspase 8 expression was unchanged or slightly upregulated (19 of 27 cases). The combination of IHC and Western blot analysis showed expression of the proforms of caspases 7, 8, and 9 in HT29-19A and HT29-16E colonic carcinoma cell lines. Apoptosis could be induced by staurosporine in both HT29 cell lines, with a sensitivity similar to that of the HGT cell line, but lower than that of the DAUDI cell line. Apoptosis induction in HT29 cells was concomitant with processing of caspases 3, 7, 8, and 9 and was inhibited by the caspase inhibitor ZVAD. Our data show that (1) human colon cancer cells downregulate caspase 7 and, to a smaller extent, caspase 9 in vivo and (2) in vitro staurosporine-induced apoptosis of colonic cancer cells involves caspases 7 and 9. Caspase 7 deficiency thus appears as a new immunohistochemical marker of colonic neoplasia; its correction represents a potential basis for new therapies.
Palmerini
F
F
INSERM U 119; Department of Pathology, Institut Paoli-Calmettes, IFR 57 and Université de la Méditerranée, Marseille, France.
Devilard
E
E
Jarry
A
A
Birg
F
F
Xerri
L
L
D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000032:analysis* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; C505520:CASP7 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D019311:Staurosporine; D004121:Dimethyl Sulfoxide