Expression of cellular FLICE-inhibitory protein and its association with p53 mutation in colon cancer.

Abstract

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.

• Authors: Xiao-Dong Zhou, Jie-Ping Yu, Hong-Xia Chen, Hong-Gang Yu, He-Sheng Luo
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 11 Issue 16 Pg. 2482-5 (Apr 28 2005) ISSN: 1007-9327 [Print] United States
• PMID: 15832422 (Publication Type: Journal Article)

Chemical References

• CASP8 and FADD-Like Apoptosis Regulating Protein
• CFLAR protein, human
• Intracellular Signaling Peptides and Proteins
• RNA, Messenger
• Tumor Suppressor Protein p53

Topics

• Adult
• Aged
• Aged, 80 and over
• CASP8 and FADD-Like Apoptosis Regulating Protein
• Colonic Neoplasms (genetics, metabolism, physiopathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Male
• Middle Aged
• Mutation
• RNA, Messenger (analysis)
• Tumor Suppressor Protein p53 (genetics, metabolism)