Frizzled-1 is down-regulated in follicular thyroid tumours and modulates growth and invasiveness

A Ulivieri1, L Lavra, R Dominici

  • 1Research Centre, S. Pietro Fatebenefratelli Hospital, Rome, Italy.

The Journal of Pathology
|February 29, 2008
PubMed

Insights

Loss of Frizzled-1 (FZD-1) gene expression is common in follicular thyroid tumors, suggesting its role in tumor growth and potential as a diagnostic marker.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Follicular thyroid carcinoma (FTC) development mechanisms are unclear.
  • Loss of heterozygosity (LOH) at 7q21 is frequent in FTC.
  • Investigating gene expression changes associated with LOH is crucial.

Purpose of the Study:

  • To analyze the impact of LOH on gene expression in thyroid lesions.
  • To identify specific genes within the 7q21 region involved in follicular tumor progression.
  • To evaluate the role of Frizzled-1 (FZD-1) in follicular thyroid tumor pathogenesis.

Main Methods:

  • Analysis of mRNA expression of six genes at 7q21.1-7q21.3 in 23 thyroid lesions (hyperplasias, adenomas, FTCs, PTCs).
  • Quantitative RT-PCR on an independent series of 69 follicular neoplastic lesions and 25 PTCs.
  • In vitro studies using FTC- and PTC-derived cell lines to assess FZD-1 protein and mRNA levels, invasiveness, and proliferation.

Main Results:

  • Frizzled-1 (FZD-1) gene exhibited the lowest mRNA expression among the analyzed genes.
  • FZD-1 down-regulation was confirmed in follicular neoplastic lesions and FTC cell lines.
  • Overexpression of FZD-1 reduced invasiveness and proliferation in FTC cells; RNA interference increased invasiveness in PTC cells.

Conclusions:

  • FZD-1 plays a significant role in the growth and progression of follicular thyroid tumors.
  • Reduced FZD-1 expression is a key event in follicular tumorigenesis.
  • FZD-1 may serve as a novel diagnostic marker for follicular thyroid tumors.

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