Hras G12V induces follicular thyroid cancer with attenuated MAPK activation and increased latency compared to Kras G12D
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Le résumé fourni par la source
Abstract RAS mutations are found in nearly 50% of follicular thyroid cancers (FTCs), frequently accompanied by secondary mutations in the PI3K/AKT pathway as tumors advance to more poorly differentiated states. To examine the role that oncogenic Hras plays in thyroid tumor initiation and progression, we developed murine models with thyroid-specific expression of Hras G12V combined with heterozygous or homozygous loss of Pten. Loss of Pten cooperated with Hras G12V in a dose-dependent manner to induce the development of follicular thyroid carcinoma and poorly-differentiated thyroid carcinoma. Histopathology of Hras G12V /Pten Hom tumors closely resembled those from the established Kras G12D /Pten Hom model, but tumor onset was significantly delayed in Hras G12V /Pten Hom mice. At three weeks of age, downregulation of MAPK pathway inhibitors was observed in Kras G12D /Pten Hom thyroids, accompanied by increased MAPK pathway activation compared to Hras G12V /Pten Hom mice. Furthermore, amplification of oncogenic Ras was found in Hras G12V tumors and cell lines, while allelic balance was maintained in Kras G12D models. These studies demonstrate clear phenotypic differences between mutant Hras and Kras in the thyroid and suggest that delayed MAPK activation may mediate the increased tumor latency observed in the Hras G12V /Pten Hom model.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- <i> Hras <sup>G12V</sup> </i> induces follicular thyroid cancer with attenuated MAPK activation and increased latency compared to <i> Kras <sup>G12D</sup> </i>
- Date Crossref
- 15/09/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Children's Hospital of Philadelphia Department of Pediatrics pays non établi dans la noticeOrganisme public
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University of Arkansas for Medical Sciences Department of Physiology and Biophysics pays non établi dans la noticeUniversité ou école supérieure
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Winthrop Rockefeller Foundation pays non établi dans la noticeOrganisation à but non lucratif
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Albert Einstein College of Medicine Department of Developmental and Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
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University of Pennsylvania Abramson Cancer Center pays non établi dans la noticeUniversité ou école supérieure
Department of Pediatrics — Children's Hospital of Philadelphia, Department of Physiology and Biophysics — University of Arkansas for Medical Sciences et Winthrop Rockefeller Foundation, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.