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Accepted Preprint first posted online on 4 March 2009

Endocrine-Related Cancer 2009;16:483.

DOI: 10.1677/ERC-08-0272
Copyright © 2009 by the Society for Endocrinology.
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RESEARCH

Impairment of the p27KIP1 function enhances thyroid carcinogenesis in TRK-T1 transgenic mice

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

M Fedele, Istituto di Endocrinologia e Oncologia Sperimentale (IEOS) del CNR, Naples, Italy
D Palmieri, Dipartimento di Biologia e Patologia Cellulaire e Molecolare, University of Naples 'Federico II', Naples, Italy
G Chiappetta, Oncologia sperimentale, INT Fondazione Pascale, Napoli, Italy
R Pasquinelli, Oncologia sperimentale, INT Fondazione Pascale, Napoli, Italy
I De Martino, Dipartimento di Biologia e Patologia Cellulaire e Molecolare, University of Naples 'Federico II', Naples, Italy
C Arra, Animal Facility, INT Fondazione Pascale, Naples, Italy
G Palma, Animal Facility, INT Fondazione Pascale, Naples, Italy
T Valentino, Dipartimento di Biologia e Patologia Cellulaire e Molecolare, University of Naples 'Federico II', Naples, Italy
G Pierantoni, Dipartimento di Biologia e Patologia Cellulaire e Molecolare, University of Naples 'Federico II', Naples, Italy
G Viglietto, Medicina Sperimentale e Clinica, Universita' Magna Graecia, Catanzaro, Italy
J Rothstein, Inflammation Research, Amgen Inc., Seattle, United States
M Santoro, Dipartimento di Biologia e Patologia Cellulaire e Molecolare, University of Naples 'Federico II', Naples, Italy
A Fusco, Istituto di Endocrinologia e Oncologia Sperimentale (IEOS) del CNR, Naples, Italy

Correspondence: Alfredo Fusco, Email: afusco{at}napoli.com

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 to p27kip1 wild-type compounds (TRK-T1/p27p27+/+). 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.






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