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

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. © 2009 Society for Endocrinology.