PIN1 gene overexpression and beta-catenin gene mutation/expression in hepatocellular carcinoma and their significance.
The evolution of hepatocellular carcinoma (HCC) is a compound process which involves many kinds of genes and transductional pathways. The expression of the peptidyl-proplyl-isomerase PIN1 gene, the mutation in exon 3 of beta-catenin and its correspondent abnormal expression and their roles in the hepatocellular carcinogeneisis were investigated. Among 29 pair cases of HCC and non-carcinoma tissues, the expression of PIN1 gene was detected by immunochemical staining. Mutations in exon 3 of beta-catenin gene and differential expression of beta-catenin gene were investigated by the methods of PCR-SSCP, direct sequencing and immunohistochemical technique as well. The results indicated: (1) 44.8% (13/29) cases of HCC presented higher level of PIN1 gene expression than non-cancerous tissues (chi2=32.63, P<0.05), especially in cytoplasm and nucleus, while there was lower level of PIN1 expression in non-cancerous tissues; (2) 58.6% (17/29) HCC tissues showed beta-catenin protein accumulation in cytoplasm and nucleus. 46.2% (6/13) HCC tissues indicated beta-catenin protein accumulation with higher level of PIN1 expression, while 53.8% (7/13) HCC tissues indicated beta-catenin protein accumulation with lower level or trace of PIN1 expression (chi2=0.00, P>0.05); (3) 24.1% (7/29) of primary tumor lesions carried gene mutations in exon 3 of beta-catenin, and accompanied by beta-catenin protein accumulation. There was no mutation in non-cancerous tissues. All the mutation presented in tissues with low level of PIN1 expression. There was no mutation of beta-catenin gene in tissues with high PIN1 expression level (chi2=58.12, P<0.05). So it was postulated that the increase of PIN1 gene expression could promote hepatocellular carcinogenesis via a way different from beta-catenin gene mutation.
Wang
Hui
H
Department of Medical Genetics, School of Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. huiwang1977@yahoo.com.cn
Zhang
Jinxiang
J
Feng
Wei
W
Zhang
Shu
S
Liang
Huifang
H
Wang
Yang
Y
Zheng
Qichang
Q
Li
Zhuoya
Z
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics*
D004273:DNA, Neoplasm; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D051176:beta Catenin; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase