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Novel oncogenic actions of TRbeta mutants in tumorigenesis

Celine J Guigon1, Sheue-yann Cheng

  • 1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4264, USA.

IUBMB Life
|April 25, 2009
PubMed

Insights

Thyroid hormone receptor beta (TRbeta) mutations contribute to cancer development. A mouse model revealed TRbeta mutants drive thyroid and pituitary tumors through genomic and nongenomic pathways.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Thyroid hormone (T3) is crucial for metabolism, growth, and differentiation.
  • Germline mutations in thyroid hormone receptor beta (TRbeta) cause resistance to thyroid hormone.
  • Somatic TRbeta mutations are increasingly linked to human cancers, but their in vivo role in carcinogenesis is unclear.

Purpose of the Study:

  • To investigate the in vivo molecular actions of TRbeta mutants in carcinogenesis.
  • To understand the role of TRbeta mutations in the development of thyroid and pituitary tumors.

Main Methods:

  • Creation of a mouse model (TRbeta(PV/PV)) with a knockin TRbeta mutation (TRbetaPV).
  • Phenotypic analysis of TRbeta(PV/PV) mice to study tumor development.
  • Investigation of genomic and nongenomic mechanisms underlying TRbeta mutant activity.

Main Results:

  • TRbeta(PV/PV) mice exhibited a striking phenotype of thyroid cancer and pituitary tumors.
  • The TRbetaPV mutant demonstrated novel functions in tumorigenesis.
  • The oncogenic action of TRbetaPV was found to be mediated by both genomic and nongenomic pathways.

Conclusions:

  • TRbeta mutants play a significant role in tumorigenesis.
  • TRbetaPV's oncogenic effects involve alterations in gene expression and signaling pathways via both genomic and nongenomic mechanisms.
  • This study provides in vivo evidence for the involvement of TRbeta mutants in cancer development.

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