Caspase 7 downregulation as an immunohistochemical marker of colonic carcinoma

Caspases play a crucial role as apoptotic effecters; their potential implic ation in tumorigenesis remains to be clarified. We investigated the express ion and function of caspases 7, 8, and 9 in colon cancer tissues and cell l ines. Immunohistochemistry (MC) showed downregulation of caspase 7 (22 of 2 6 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 unc hanged 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 coul d be induced by staurosporine in both HT29 cell lines, with a sensitivity s imilar 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. Ou r data show that (1) human colon cancer cells downregulate caspase 7 and, t o a smaller extent, caspase 9 in vivo and (2) in vitro staurosporine-induce d apoptosis of colonic cancer cells involves caspases 7 and 9. Caspase 7 de ficiency thus appears as a new immunohistochemical marker of colonic neopla sia; its correction represents a potential basis for new therapies. Copyrig ht (C) 2001 by W.B. Saunders Company.