Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas

D. Vitagliano, G. Portella, G. Troncone, A. Francione, C. Rossi, A. Bruno, A. Giorgini, S. Coluzzi, T. C. Nappi, J. L. Rothstein, R. Pasquinelli, G. Chiappetta, D. Terracciano, V. Macchia, R. M. Melillo, A. Fusco, M. Santoro

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Abstract

Ras oncogenes are frequently mutated in thyroid carcinomas. To verify the role played by N-ras in thyroid carcinogenesis, we generated transgenic mice in which a human N-ras(Gln61Lys) oncogene (Tg-N-ras) was expressed in the thyroid follicular cells. Tg-N-ras mice developed thyroid follicular neoplasms; 11% developed follicular adenomas and ∼40% developed invasive follicular carcinomas, in some cases with a mixed papillary/follicular morphology. About 25% of the Tg-N-ras carcinomas displayed large, poorly differentiated areas, featuring vascular invasion and forming lung, bone or liver distant metastases. N-ras(Gln61Lys) expression in cultured PC Cl 3 thyrocytes induced thyroid-stimulating hormone-independent proliferation and genomic instability with micronuclei formation and centrosome amplification. These findings support the notion that mutated ras oncogenes could be able to drive the formation of thyroid tumors that can progress to poorly differentiated, metastatic carcinomas.

Original languageEnglish
Pages (from-to)5467-5474
Number of pages8
JournalOncogene
Volume25
Issue number39
DOIs
Publication statusPublished - Aug 31 2006

Fingerprint

ras Genes
Transgenic Mice
Thyroid Gland
Carcinoma
Thyroid Neoplasms
Neoplasms
Centrosome
Genomic Instability
Thyrotropin
Adenoma
Blood Vessels
Carcinogenesis
Neoplasm Metastasis
Bone and Bones
Lung
Liver
Thyroid Epithelial Cells

Keywords

  • Carcinoma
  • Differentiation
  • Kinase
  • Progression
  • Ras
  • Thyroid

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas. / Vitagliano, D.; Portella, G.; Troncone, G.; Francione, A.; Rossi, C.; Bruno, A.; Giorgini, A.; Coluzzi, S.; Nappi, T. C.; Rothstein, J. L.; Pasquinelli, R.; Chiappetta, G.; Terracciano, D.; Macchia, V.; Melillo, R. M.; Fusco, A.; Santoro, M.

In: Oncogene, Vol. 25, No. 39, 31.08.2006, p. 5467-5474.

Research output: Contribution to journalArticle

Vitagliano, D, Portella, G, Troncone, G, Francione, A, Rossi, C, Bruno, A, Giorgini, A, Coluzzi, S, Nappi, TC, Rothstein, JL, Pasquinelli, R, Chiappetta, G, Terracciano, D, Macchia, V, Melillo, RM, Fusco, A & Santoro, M 2006, 'Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas', Oncogene, vol. 25, no. 39, pp. 5467-5474. https://doi.org/10.1038/sj.onc.1209527
Vitagliano, D. ; Portella, G. ; Troncone, G. ; Francione, A. ; Rossi, C. ; Bruno, A. ; Giorgini, A. ; Coluzzi, S. ; Nappi, T. C. ; Rothstein, J. L. ; Pasquinelli, R. ; Chiappetta, G. ; Terracciano, D. ; Macchia, V. ; Melillo, R. M. ; Fusco, A. ; Santoro, M. / Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas. In: Oncogene. 2006 ; Vol. 25, No. 39. pp. 5467-5474.
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