title: Impairment of the p27kip1 function enhances thyroid carcinogenesis in TRK-T1 transgenic mice.
abstract: Impairment of the p27(kip1) function, caused by a drastic reduction of its expression or cytoplasmic mislocalization, has been frequently observed in thyroid carcinomas. To understand the role of p27(kip1) impairment in thyroid carcinogenesis, we investigated the consequences of the loss of p27(kip1) 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 p27(kip1) null allele (TRK-T1/p27(-/-)) display a higher incidence of papillary thyroid carcinomas, with a shorter latency period and increased proliferation index, compared with p27(kip1) wild-type compounds (TRK-T1/p27(+/+)). Consistently, double mutant mice heterozygous for a p27(kip1) 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 p27(kip1) function in papillary thyroid cancer development.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, 80131 Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Fedele
authors.forename: Dario
authors.initials: D
authors.lastname: Palmieri
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.forename: Rosa
authors.initials: R
authors.lastname: Pasquinelli
authors.forename: Ivana
authors.initials: I
authors.lastname: De Martino
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palma
authors.forename: Teresa
authors.initials: T
authors.lastname: Valentino
authors.forename: Giovanna M
authors.initials: GM
authors.lastname: Pierantoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viglietto
authors.forename: Jay L
authors.initials: JL
authors.lastname: Rothstein
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology*; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000502:physiology*; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C493961:Cdkn1b protein, mouse; D015513:Oncogene Proteins; C065400:oncogene protein trk; D050760:Cyclin-Dependent Kinase Inhibitor p27