Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis.
The molecular genetic basis of thyroid carcinogenesis is not well understood. Most of the existing models of thyroid cancer only rarely show metastases, and this has limited progress in the understanding of the molecular events in thyroid cancer invasion and metastasis. We have recently generated a mutant mouse by introducing a dominant negative mutant thyroid hormone nuclear receptor gene, TRbetaPV, into the TRbeta gene locus. In this TRbetaPV mouse, the regulation of the thyroid-pituitary axis is disrupted, leading to a mouse with high levels of circulating thyroid-stimulating hormone and extensive hyperplasia of follicular epithelium within the thyroid. As TRbeta(PV/PV) mice, but not TRbeta(PV/+) mice, aged, metastatic thyroid carcinoma developed. Histologic evaluation of thyroids of 5-14-month-old mice showed capsular invasion (91%), vascular invasion (74%), anaplasia (35%), and metastasis to the lung and heart (30%). Previous models of thyroid cancer have focused on genes that control initial carcinogenesis, but this model provides an unusual opportunity to study the alterations in gene regulation that occur with clinically relevant changes during progression and metastasis in a predictable fashion.
Suzuki
Hideyo
H
Gene Regulation Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-4264, USA.
Willingham
Mark C
MC
Cheng
Sheue-Yann
SY
D000708:Anaplasia; D000818:Animals; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D004195:Disease Models, Animal; D018450:Disease Progression; D006965:Hyperplasia; D051379:Mice; D008817:Mice, Mutant Strains; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D037042:Thyroid Hormone Receptors beta; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
D011988:Receptors, Thyroid Hormone; D037042:Thyroid Hormone Receptors beta