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Published on: August 23, 2019
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.
Abstract:
The mechanisms of follicular thyroid carcinoma (FTC) transformation and progression are not well understood. Previously, we detected LOH at 7q21 in all FTCs examined, indicating that loss of genetic material in that region is a common trait in these lesions. To analyse the effects of LOH on gene expression, we performed an analysis of the mRNA expression levels of six different genes, located at 7q21.1-7q21.3. A total of 23 lesions, including eight follicular hyperplasias (FHs), eight follicular adenomas (FAs), two FTCs and five papillary thyroid carcinomas (PTCs) were analysed. The Frizzled-1 (FZD-1) gene, located at 7q21.13, showed the lowest levels of mRNA expression. Down-regulation of FZD-1 expression was also confirmed in an independent series of 69 follicular neoplastic lesions compared to 25 PTCs, analysed by quantitative RT-PCR. In vitro studies showed that FZD-1 expression was also markedly reduced at both protein and mRNA levels in three FTC-derived cell lines (FRO, WRO and FTC-133), while it was normal in the three PTC-derived cell lines (Ca300, Ca301 and K1) examined. We demonstrated that over-expression of FZD-1 in 3 FTC-derived cells decreased invasiveness and proliferation rate, indicating a possible pathogenetic role. In addition, FZD-1 RNA interference in the PTC-derived cell line K1 increased invasiveness. Our data indicated that FZD-1 is involved in growth of follicular tumours and may be considered as a novel marker of this type of tumour.
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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