Published online Apr 28, 2005. doi: 10.3748/wjg.v11.i16.2482
Revised: March 14, 2004
Accepted: April 7, 2004
Published online: April 28, 2005
AIM: To investigate the expression of cellular FLICE (Fas associated death domain-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) and its association with p53 mutation in colon cancer.
METHODS: Immunohistochemical staining of c-FLIP and mutant p53 by using specific antibodies was performed by the standard streptavidin-peroxidase technique for 45 colon cancer tissue samples with matched normal tissues. Semi-quantitative reverse transcriptional (RT)-PCR was used to measure c-FLIP mRNA levels. t-test statistical method was used in data analyses.
RESULTS: c-FLIP mRNA was expressed in all colon cancer tissues and its level (0.63±0.12) was significantly higher than that in normal tissues (0.38±0.10, P<0.01). Immuno-histochemically, c-FLIP protein was also expressed in all colon cancers (45/45) and 71.1% (32/45) showed an intense immunostaining, in contrast, 93.3% (42/45) of normal colonic mucosa showed positive staining and none of them immunostained intensely. The quantity of c-FLIP protein was significantly higher in cancer tissues than in normal mucosa (7.04±1.20 vs 5.21±0.86, P<0.01). Positive staining of mutant p53 protein was found in 60% (27/45) colon cancers. c-FLIP mRNA level was decreased in p53 positive group compared with p53 negative cancer tissues (0.59±0.13 vs 0.69±0.14, P<0.01), but c-FLIP protein had a significantly higher level in p53 positive cancer tissues than in negative ones (7.57±1.30 vs 6.25±1.27, P<0.01).
CONCLUSION: c-FLIP is specially overexpressed in colon cancers and it might contribute to carcinogenesis of normal colonic mucosa. p53 may exert transcriptional upregulation effects on c-FLIP gene and more potent effects on promoting the degradation of c-FLIP protein.