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Related Experiment Videos

Thyroid carcinomas in RET/PTC transgenic mice.

S M Jhiang1, J Y Cho, T L Furminger

  • 1Department of Physiology, Ohio State University, Columbus 43210, USA.

Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progres Dans Les Recherches Sur Le Cancer
|February 23, 1999
PubMed
Summary

The RET/PTC oncogene drives papillary thyroid cancer development in mice. Specific signaling pathways mediated by RET/PTC1

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Genetic alterations in thyroid cancer: the role of mouse models.

Veterinary pathology·2007

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The RET/PTC oncogene, a rearranged form of the RET proto-oncogene, is linked to human papillary thyroid carcinomas.
  • Understanding the oncogenic role of RET/PTC is crucial for thyroid cancer research.

Purpose of the Study:

  • To investigate if RET/PTC causes papillary thyroid carcinoma.
  • To identify the signaling pathways essential for RET/PTC-induced thyroid tumor development.
  • To compare the aggressiveness of RET/PTC1 and RET/PTC3 in thyroid tumorigenesis.

Main Methods:

  • Generation of transgenic mouse models with targeted thyroid expression of RET/PTC1, RET/PTC1 triple mutant, and RET/PTC3.
  • Analysis of tumor characteristics, including growth rate, TSH-responsiveness, and radioiodide uptake.

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  • Assessment of cellular abnormalities and proliferation rates in embryonic and adult transgenic mice.

    • Main Results:

    • RET/PTC1 transgenic mice developed thyroid tumors with slow growth, TSH-dependent progression, and loss of radioiodide uptake.
    • Tumor onset and severity correlated with RET/PTC1 expression levels.
    • A RET/PTC1 triple mutant lacking key phosphotyrosine binding sites failed to induce thyroid abnormalities, indicating the importance of these sites in oncogenesis.
    • RET/PTC3 transgenic mice were generated for comparative aggressiveness studies.

    Conclusions:

    • RET/PTC1 expression in the thyroid gland is sufficient to induce papillary thyroid carcinoma in mice.
    • Specific phosphotyrosine signaling pathways mediated by RET/PTC1 are essential for thyroid tumor development.
    • The generated mouse models provide valuable tools for studying thyroid cancer pathogenesis and evaluating therapeutic strategies.