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


CONCLUSIONS
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.
Zhou
Xiao-Dong
XD
Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang road 238, Wuhan 430060, Hubei Province, China. zhouxd7612@hotmail.com
Yu
Jie-Ping
JP
Chen
Hong-Xia
HX
Yu
Hong-Gang
HG
Luo
He-Sheng
HS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53