Association of hTcf-4 gene expression and mutation with clinicopathological characteristics of hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma(HCC) is a significant health problem in China. But the molecular mechanisms of HCC remains unclear. APC/beta-Catenin/Tcf signaling pathway, also known as Wnt pathway, plays a critical role in the development and oncogenesis. As little is known about the alteration of human T-cell transcription factor-4 (hTcf-4) gene in HCC, it is of interest to study the expression and mutation of hTcf-4 gene in HCC and the relationship between hTcf-4 gene and progression of HCC.


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the expression of hTcf-4 mRNA in 32 HCC and para-cancerous tissues and 5 normal liver tissues. PCR-single strand conformation polymorphism (PCR-SSCP) method was used to detect the mutation of hTcf-4 exons 1, 4, 9 and 15 in HCC. The correlation of expression and mutation of the hTcf-4 gene with clinicopathological characteristics of HCC was also analyzed.


RESULTS
RT-PCR showed that the expression rate of hTcf-4 mRNA in HCC, para-cancerous tissues and normal liver tissues was 90.6 %, 71.9 % and 80 %, respectively. The gene expression level in tumor was 0.71+/-0.13, much higher than that in para-cancerous liver 0.29+/-0.05 and normal liver 0.26+/-0.05 (P<0.001), although there was no significant difference in gene expression level between para-cancerous tissues and normal liver (P>0.05). Furthermore, hTcf-4 gene expression was closely associated with tumor capsule status and intrahepatic metastasis of HCC. On SSCP, 2 of 32 cases of HCC (6.25 %) displayed characteristic mutational mobility shifts in exon 15 of the hTcf-4 gene. No abnormal shifting bands were observed in para-cancerous tissues.


CONCLUSIONS
The high expression level of hTcf-4 in HCC, especially in tumors with metastasis, suggests that the over-expression of hTcf-4 gene may be closely associated with development and progression of HCC, but the mutation of this gene seemed to play less important role in this respect.
Jiang
Ying
Y
Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai 200032, China.
Zhou
Xin-Da
XD
Liu
Yin-Kun
YK
Wu
Xin
X
Huang
Xiao-Wu
XW
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000502:physiology; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D016622:Silver Staining; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics*
D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors