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PMID: 12378619 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Association of hTcf-4 gene expression and mutation with clinicopathological characteristics of hepatocellular carcinoma.

World journal of gastroenterology ·Vol. 8 ·No. 5 ·2002-10-00 ·Pages 804-7

Jiang Y, Zhou XD, Liu YK, Wu X, Huang XW

Abstract

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. 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. 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. 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.

MeSH Terms
Adolescent Adult Aged Carcinoma, Hepatocellular/pathology,physiopathology Female Gene Expression Regulation, Neoplastic Humans Liver/physiology Liver Neoplasms/pathology,physiopathology Male Middle Aged Mutation Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational RNA, Messenger/analysis Silver Staining TCF Transcription Factors Transcription Factor 7-Like 2 Protein Transcription Factors/genetics
Chemicals
RNA, Messenger TCF Transcription Factors TCF7L2 protein, human Transcription Factor 7-Like 2 Protein Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Jiang Ying
Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai 200032, China.
Zhou Xin-Da
Liu Yin-Kun
Wu Xin
Huang Xiao-Wu
References (43)
43 references, click to expand
  1. Identification of c-MYC as a target of the APC pathway.
    Science. 1998 Sep 4;281(5382):1509-12 PMID: 9727977
  2. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
    Science. 1997 Mar 21;275(5307):1784-7 PMID: 9065401
  3. The Yin-Yang of TCF/beta-catenin signaling.
    Adv Cancer Res. 2000;77:1-24 PMID: 10549354
  4. Wnt signaling controls the phosphorylation status of beta-catenin.
    J Biol Chem. 2002 May 17;277(20):17901-5 PMID: 11834740
  5. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway.
    Proc Natl Acad Sci U S A. 1999 May 11;96(10):5522-7 PMID: 10318916
  6. Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3 mutations in malignant melanoma.
    Am J Pathol. 1999 Feb;154(2):325-9 PMID: 10027390
  7. Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex.
    Genes Dev. 1999 Jul 15;13(14):1768-73 PMID: 10421629
  8. Beta-catenin activation through mutation is rare in rectal cancer.
    Cancer Genet Cytogenet. 2001 Jul 1;128(1):43-5 PMID: 11454429
  9. Bridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-mediated transcription.
    Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3020-3 PMID: 9501208
  10. Polymorphisms in cyclin D1 gene and hepatocellular carcinoma.
    Mol Carcinog. 2002 Feb;33(2):125-9 PMID: 11813305
  11. Variable mutation frequencies in coding repeats of TCF-4 and other target genes in colon, gastric and endometrial carcinoma showing microsatellite instability.
    Oncogene. 1999 Nov 18;18(48):6806-9 PMID: 10597289
  12. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer.
    Cancer Res. 1998 Mar 15;58(6):1130-4 PMID: 9515795
  13. Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations.
    Cancer Res. 1998 Mar 1;58(5):1021-6 PMID: 9500465
  14. Wnt signalling in mammalian development and cancer.
    Cancer Metastasis Rev. 1999;18(2):215-30 PMID: 10728985
  15. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly.
    Science. 1996 May 17;272(5264):1023-6 PMID: 8638126
  16. Constitutive activation of Wnt/beta-catenin signaling pathway in migration-active melanoma cells: role of LEF-1 in melanoma with increased metastatic potential.
    Biochem Biophys Res Commun. 2001 Oct 19;288(1):8-15 PMID: 11594745
  17. Nuclear translocation of beta-catenin in colorectal cancer.
    Br J Cancer. 2000 May;82(10):1689-93 PMID: 10817505
  18. Cadherins and catenins in development.
    Curr Opin Cell Biol. 1996 Oct;8(5):685-91 PMID: 8939663
  19. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.
    Science. 1997 Mar 21;275(5307):1787-90 PMID: 9065402
  20. The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines.
    Cancer Res. 2000 Jul 15;60(14):3872-9 PMID: 10919662
  21. Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin.
    Science. 1999 Mar 12;283(5408):1739-42 PMID: 10073940
  22. Regulatory region of metastasis-inducing DNA is the binding site for T cell factor-4.
    Oncogene. 2001 Mar 29;20(14):1793-7 PMID: 11313926
  23. E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesion-independent manner.
    J Cell Biol. 2001 May 28;153(5):1049-60 PMID: 11381089
  24. Frequent frameshift mutations of the TCF-4 gene in colorectal cancers with microsatellite instability.
    Cancer Res. 1999 Sep 1;59(17):4213-5 PMID: 10485457
  25. Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.
    Science. 1998 Apr 24;280(5363):596-9 PMID: 9554852
  26. TCF-4 binds beta-catenin and is expressed in distinct regions of the embryonic brain and limbs.
    Mech Dev. 1998 Sep;77(1):9-18 PMID: 9784592
  27. Hepatocellular carcinoma results from chronic cyclin D1 overexpression in transgenic mice.
    Cancer Res. 2001 Jul 15;61(14):5389-95 PMID: 11454681
  28. Correlation of c-myc overexpression and amplification with progression of preneoplastic liver lesions to malignancy in the poorly susceptible Wistar rat strain.
    Mol Carcinog. 1999 May;25(1):21-9 PMID: 10331741
  29. Frequent alterations of the beta-catenin and TCF-4 genes, but not of the APC gene, in colon cancers with high-frequency microsatellite instability.
    J Exp Clin Cancer Res. 2001 Dec;20(4):553-9 PMID: 11876551
  30. The prognostic molecular markers in hepatocellular carcinoma.
    World J Gastroenterol. 2002 Jun;8(3):385-92 PMID: 12046056
  31. Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma.
    J Gastroenterol. 1999 Aug;34(4):486-93 PMID: 10452682
  32. Genetic alterations in the human Tcf-4 gene in Japanese patients with sporadic gastrointestinal cancers with microsatellite instability.
    Oncology. 2001;61(2):156-61 PMID: 11528255
  33. A possible role for the high mobility group box transcription factor Tcf-4 in vertebrate gut epithelial cell differentiation.
    J Biol Chem. 1999 Jan 15;274(3):1566-72 PMID: 9880534
  34. Loss of beta-catenin regulation by the APC tumor suppressor protein correlates with loss of structure due to common somatic mutations of the gene.
    Cancer Res. 1997 Oct 15;57(20):4624-30 PMID: 9377578
  35. Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3.
    Cytogenet Cell Genet. 2000;88(3-4):264-5 PMID: 10828605
  36. Cyclin D1 overexpression in hepatocellular carcinoma.
    Liver. 2001 Apr;21(2):89-95 PMID: 11318977
  37. Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium.
    Am J Pathol. 1999 Jan;154(1):29-35 PMID: 9916915
  38. Functional interaction of beta-catenin with the transcription factor LEF-1.
    Nature. 1996 Aug 15;382(6592):638-42 PMID: 8757136
  39. The LEF1/beta -catenin complex activates movo1, a mouse homolog of Drosophila ovo required for epidermal appendage differentiation.
    Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6064-9 PMID: 11983900
  40. Amplification of c-myc in hepatocellular carcinoma: correlation with clinicopathologic features, proliferative activity and p53 overexpression.
    Oncology. 1999;57(2):157-63 PMID: 10461064
  41. TCF transcription factors: molecular switches in carcinogenesis.
    Biochim Biophys Acta. 1999 Oct 29;1424(2-3):M23-37 PMID: 10528152
  42. Complex formation of adenomatous polyposis coli gene product and axin facilitates glycogen synthase kinase-3 beta-dependent phosphorylation of beta-catenin and down-regulates beta-catenin.
    J Biol Chem. 2000 Nov 3;275(44):34399-406 PMID: 10906131
  43. Metastasis-inducing dna regulates the expression of the osteopontin gene by binding the transcription factor Tcf-4.
    Cancer Res. 2001 Jul 15;61(14):5619-29 PMID: 11454716
Article Info
Journal
World journal of gastroenterology
Abbr.
World J Gastroenterol
ISSN
1007-9327
DOI
10.3748/wjg.v8.i5.804
Published
2002-10-00
Pages
804-7
Language
English
Region
United States
NLM ID
100883448
PMCID
PMC4656565
Subset
IM
External Links
PubMed source DOI: 10.3748/wjg.v8.i5.804 PMC Full Text View journal details
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