Skip to main content
Journal cover image

Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma.

Publication ,  Journal Article
Merle, P; Kim, M; Herrmann, M; Gupte, A; Lefrançois, L; Califano, S; Trépo, C; Tanaka, S; Vitvitski, L; de la Monte, S; Wands, JR
Published in: J Hepatol
November 2005

BACKGROUND/AIMS: The molecular mechanisms of hepatocarcinogenesis remain largely unknown. Previous studies suggest that activation of the Wnt/beta-catenin pathway is important during hepatocyte transformation but the role of Frizzled receptor (FZD) in this process has not been defined. Here we investigate activation of this pathway by FZD using transgenic hepatocellular carcinoma (HCC) murine models. METHODS: We employed single (c-myc, SV40-Tag) and established double [insulin receptor substrate-1 (IRS-1/c-myc) and hepatitis Bx protein (X/c-myc)] transgenic lines and all developed HCC. Expression of 9 FZD was measured by real time RT-PCR and Western blot analysis. Phosphorylation and cellular accumulation of beta-catenin were assessed in both dysplastic tissue and tumors. We investigated the effect of a dominant negative (DN) FZD7 on TCF transcriptional activity in a SV40 derived HCC cell line. RESULTS: FZD7 was highly overexpressed at the mRNA and protein level(s) in HCC and occurred in dysplasia. Upregulation of FZD7 was associated with reduced phosphorylation of beta-catenin and led to nuclear accumulation in HCC tumors. Ectopic expression of a DN FZD7 construct decreased TCF transcriptional activity in tumor cells. CONCLUSIONS: These observations suggest that upregulation of FZD7 receptors in association with activation of the canonical Wnt/beta-catenin pathway is a common molecular event in HCC.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Hepatol

DOI

ISSN

0168-8278

Publication Date

November 2005

Volume

43

Issue

5

Start / End Page

854 / 862

Location

Netherlands

Related Subject Headings

  • beta Catenin
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • RNA, Messenger
  • Phosphorylation
  • Oncogenes
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Merle, P., Kim, M., Herrmann, M., Gupte, A., Lefrançois, L., Califano, S., … Wands, J. R. (2005). Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma. J Hepatol, 43(5), 854–862. https://doi.org/10.1016/j.jhep.2005.05.018
Merle, Philippe, Miran Kim, Marc Herrmann, Anand Gupte, Lydie Lefrançois, Sophia Califano, Christian Trépo, et al. “Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma.J Hepatol 43, no. 5 (November 2005): 854–62. https://doi.org/10.1016/j.jhep.2005.05.018.
Merle P, Kim M, Herrmann M, Gupte A, Lefrançois L, Califano S, et al. Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma. J Hepatol. 2005 Nov;43(5):854–62.
Merle, Philippe, et al. “Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma.J Hepatol, vol. 43, no. 5, Nov. 2005, pp. 854–62. Pubmed, doi:10.1016/j.jhep.2005.05.018.
Merle P, Kim M, Herrmann M, Gupte A, Lefrançois L, Califano S, Trépo C, Tanaka S, Vitvitski L, de la Monte S, Wands JR. Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma. J Hepatol. 2005 Nov;43(5):854–862.
Journal cover image

Published In

J Hepatol

DOI

ISSN

0168-8278

Publication Date

November 2005

Volume

43

Issue

5

Start / End Page

854 / 862

Location

Netherlands

Related Subject Headings

  • beta Catenin
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • RNA, Messenger
  • Phosphorylation
  • Oncogenes
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male