Related Experiment Video

Updated: Aug 7, 2026

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
07:01

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

Published on: April 17, 2013

Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice

F M Michiels1, B Caillou, M Talbot

  • 1Laboratoire d'Oncologie Moléculaire, Centre National de la Recherche Scientifique Unité de Recherche Associée 1158, Institut Gustave Roussy, Villejuif, France.

Proceedings of the National Academy of Sciences of the United States of America
|October 25, 1994
PubMed

Insights

Mutant guanine nucleotide stimulatory factor (Gs) alpha subunit causes thyroid tumors in mice. This study shows that altered cyclic adenosine monophosphate (cAMP) levels can drive thyroid cancer growth.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • The guanine nucleotide stimulatory factor (Gs) alpha subunit regulates cyclic adenosine monophosphate (cAMP) production.
  • Mutations in the Gs alpha subunit are implicated in various endocrine tumors.
  • Understanding the oncogenic potential of specific Gs alpha mutations in the thyroid is crucial.

Purpose of the Study:

  • To investigate the oncogenic potential of a specific mutant Gs alpha subunit (Arg-201-->His) in the thyroid gland.
  • To establish a transgenic mouse model for studying thyroid hyperfunction and tumorigenesis.
  • To explore the role of cAMP deregulation in thyroid epithelial growth control.

Main Methods:

  • Generation of transgenic mice expressing the mutant Arg-201-->His Gs alpha subunit transgene in thyroid epithelial cells using the bovine thyroglobulin promoter.
  • Analysis of thyroid morphology, cAMP levels, iodine uptake, and circulating thyroid hormone levels (triiodothyronine and thyroxine).

Main Results:

  • Transgenic mice developed hyperfunctioning thyroid adenomas.
  • Increased intracellular cAMP levels were observed in the affected thyroid tissue.
  • Elevated uptake of [125I]iodine and increased circulating levels of triiodothyronine and thyroxine were detected.
  • The mutant Gs alpha subunit demonstrated oncogenic activity.

Conclusions:

  • The mutant Gs alpha subunit possesses oncogenic activity in the thyroid gland.
  • Deregulation of cAMP levels by mutant Gs alpha subunit alters thyroid epithelial growth control.
  • These transgenic mice serve as valuable models for human autonomously functioning thyroid nodules.

More Related Videos

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer07:45

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Published on: May 18, 2020

High-Resolution Ultrasonography for the Analysis of Orthotopic ATC Tumors in a Genetically Engineered Mouse Model03:41

High-Resolution Ultrasonography for the Analysis of Orthotopic ATC Tumors in a Genetically Engineered Mouse Model

Published on: October 11, 2022

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...