Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice

Massimo Santoro, Gennaro Chiappetta, Aniello Cerrato, Domenico Salvatore, Li Zhang, Giovanni Manzo, Alessandro Picone, Giuseppe Portella, Giovanni Santelli, Giancarlo Vecchio, Alfredo Fusco

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Abstract

Gene rearrangements activating the RET proto-oncogene are frequently associated with human thyroid carcinomas belonging to the papillary subtype. These rearrangements cause the fusion of the tyrosine-kinase domain of RET to the 5'-terminal region of different genes creating the RET/PTC chimeric oncogenes. Here we report the generation of transgenic mice lines expressing the RET/PTC1 oncogene under the control of the thyroid specific rat thyroglobulin promoter. RET/PTC1-transgenic mice developed thyroid tumors displaying the histological aspect of papillary carcinomas. These tumors were slowly progressive and did not cause premature death of the animals. Two additional mice developed areas of thyroid hyperplasia. Immunohistochemical and reverse-transcriptase polymerase chain reaction analyses confirmed the thyroid-specific expression of the transgene. Given the frequency of activating rearrangements of RET in human papillary thyroid carcinomas we conclude that this animal system could be a good model for studying the neoplastic progression of thyroid carcinomas.

Original languageEnglish
Pages (from-to)1821-1826
Number of pages6
JournalOncogene
Volume12
Issue number8
Publication statusPublished - 1996

Fingerprint

Oncogenes
Transgenic Mice
Thyroid Gland
Thyroid Neoplasms
Factor IX
Premature Mortality
Proto-Oncogenes
Gene Rearrangement
Thyroglobulin
Papillary Carcinoma
Reverse Transcriptase Polymerase Chain Reaction
Transgenes
Protein-Tyrosine Kinases
Hyperplasia
Cause of Death
Neoplasms
Papillary Thyroid cancer
Genes

Keywords

  • Mice
  • Oncogene
  • Thyroid
  • Tyrosine-kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Santoro, M., Chiappetta, G., Cerrato, A., Salvatore, D., Zhang, L., Manzo, G., ... Fusco, A. (1996). Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice. Oncogene, 12(8), 1821-1826.

Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice. / Santoro, Massimo; Chiappetta, Gennaro; Cerrato, Aniello; Salvatore, Domenico; Zhang, Li; Manzo, Giovanni; Picone, Alessandro; Portella, Giuseppe; Santelli, Giovanni; Vecchio, Giancarlo; Fusco, Alfredo.

In: Oncogene, Vol. 12, No. 8, 1996, p. 1821-1826.

Research output: Contribution to journalArticle

Santoro, M, Chiappetta, G, Cerrato, A, Salvatore, D, Zhang, L, Manzo, G, Picone, A, Portella, G, Santelli, G, Vecchio, G & Fusco, A 1996, 'Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice', Oncogene, vol. 12, no. 8, pp. 1821-1826.
Santoro M, Chiappetta G, Cerrato A, Salvatore D, Zhang L, Manzo G et al. Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice. Oncogene. 1996;12(8):1821-1826.
Santoro, Massimo ; Chiappetta, Gennaro ; Cerrato, Aniello ; Salvatore, Domenico ; Zhang, Li ; Manzo, Giovanni ; Picone, Alessandro ; Portella, Giuseppe ; Santelli, Giovanni ; Vecchio, Giancarlo ; Fusco, Alfredo. / Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice. In: Oncogene. 1996 ; Vol. 12, No. 8. pp. 1821-1826.
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