Impairment of the p27kip1 function enhances thyroid carcinogenesis in TRK-T1 transgenic mice.
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.
Fedele
Monica
M
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, 80131 Naples, Italy.
Palmieri
Dario
D
Chiappetta
Gennaro
G
Pasquinelli
Rosa
R
De Martino
Ivana
I
Arra
Claudio
C
Palma
Giuseppe
G
Valentino
Teresa
T
Pierantoni
Giovanna M
GM
Viglietto
Giuseppe
G
Rothstein
Jay L
JL
Santoro
Massimo
M
Fusco
Alfredo
A
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*
C493961:Cdkn1b protein, mouse; D015513:Oncogene Proteins; C065400:oncogene protein trk; D050760:Cyclin-Dependent Kinase Inhibitor p27