Impairment of the p27kip1 function enhances thyroid carcinogenesis in TRK-T1 transgenic mice

Monica Fedele, Dario Palmieri, Gennaro Chiapetta, Rosa Pasquinelli, Ivana De Martino, Claudio Arra, Giuseppe Palma, Teresa Valentino, Giovanna M. Pierantoni, Giuseppe Viglietto, Jay L. Rothstein, Massimo Santoro, Alfredo Fusco

Research output: Contribution to journalArticle

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Abstract

Impairment of the p27kip1 function, caused by a drastic reduction of its expression or cytoplasmic mislocalization, has been frequently observed in thyroid carcinomas. To understand the role of p27kip1 impairment in thyroid carcinogenesis, we investigated the consequences of the loss of p27kip1 expression in the context of a mouse modeling of papillary thyroid cancer, expressing the TRK-T1 oncogene under the transcriptional control of thyroglobulin promoter. We found that double mutant mice homozygous for a p27kip1 null allele (TRK-T1/p27-/-) display a higher incidence of papillary thyroid carcinomas, with a shorter latency period and increased proliferation index, compared with p27kip1 wild-type compounds (TRK-T1/p27+/+). Consistently, double mutant mice heterozygous for a p27kip1 null allele (TRK-T1/p27+/ -) show an incidence of thyroid carcinomas that is intermediate between TRK-T1/p27-/- and TRK-T1/p27+/+ mice. Therefore, our findings suggest a dose-dependent role of p27kip1 function in papillary thyroid cancer development.

Original languageEnglish
Pages (from-to)483-490
Number of pages8
JournalEndocrine-Related Cancer
Volume16
Issue number2
DOIs
Publication statusPublished - Jun 2009

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Transgenic Mice
Thyroid Gland
Carcinogenesis
Thyroid Neoplasms
Alleles
Thyroglobulin
Incidence
Oncogenes
Papillary Thyroid cancer

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Fedele, M., Palmieri, D., Chiapetta, G., Pasquinelli, R., De Martino, I., Arra, C., ... Fusco, A. (2009). Impairment of the p27kip1 function enhances thyroid carcinogenesis in TRK-T1 transgenic mice. Endocrine-Related Cancer, 16(2), 483-490. https://doi.org/10.1677/ERC-08-0272

Impairment of the p27kip1 function enhances thyroid carcinogenesis in TRK-T1 transgenic mice. / Fedele, Monica; Palmieri, Dario; Chiapetta, Gennaro; Pasquinelli, Rosa; De Martino, Ivana; Arra, Claudio; Palma, Giuseppe; Valentino, Teresa; Pierantoni, Giovanna M.; Viglietto, Giuseppe; Rothstein, Jay L.; Santoro, Massimo; Fusco, Alfredo.

In: Endocrine-Related Cancer, Vol. 16, No. 2, 06.2009, p. 483-490.

Research output: Contribution to journalArticle

Fedele, M, Palmieri, D, Chiapetta, G, Pasquinelli, R, De Martino, I, Arra, C, Palma, G, Valentino, T, Pierantoni, GM, Viglietto, G, Rothstein, JL, Santoro, M & Fusco, A 2009, 'Impairment of the p27kip1 function enhances thyroid carcinogenesis in TRK-T1 transgenic mice', Endocrine-Related Cancer, vol. 16, no. 2, pp. 483-490. https://doi.org/10.1677/ERC-08-0272
Fedele, Monica ; Palmieri, Dario ; Chiapetta, Gennaro ; Pasquinelli, Rosa ; De Martino, Ivana ; Arra, Claudio ; Palma, Giuseppe ; Valentino, Teresa ; Pierantoni, Giovanna M. ; Viglietto, Giuseppe ; Rothstein, Jay L. ; Santoro, Massimo ; Fusco, Alfredo. / Impairment of the p27kip1 function enhances thyroid carcinogenesis in TRK-T1 transgenic mice. In: Endocrine-Related Cancer. 2009 ; Vol. 16, No. 2. pp. 483-490.
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