TY - JOUR
T1 - Establishment and characterization of cell lines from a novel mouse model of poorly differentiated thyroid carcinoma
T2 - Powerful tools for basic and preclinical research
AU - Dima, Mariavittoria
AU - Miller, Kelly A.
AU - Antico-Arciuch, Valeria Gabriela
AU - Di Cristofano, Antonio
PY - 2011/9/1
Y1 - 2011/9/1
N2 - Background: Poorly differentiated and anaplastic thyroid carcinomas have a rather poor prognosis. The development of relevant model systems to unravel in vitro and in vivo the molecular mechanisms governing the resistance of these tumors to therapy, as well as to test novel drug combinations, is a clear priority for thyroid-focused research. Methods: Several novel cell lines were established from tumors developed by mice engineered to simultaneously express a loss-of-function Pten allele and an oncogenic Kras allele. Results: Similar to most poorly differentiated thyroid tumors, these cell lines are characterized by simultaneous activation of the PI3K and MAPK pathways, by the presence of wild-type, functional p53, and by the severe downregulation of thyroid differentiation markers, including sodium-iodide symporter (NIS). Further, they display a highly glycolytic phenotype. They can be grafted to syngeneic, immunocompetent hosts, and easily metastasize to the lungs. Conclusions: These mouse cell lines are a novel and invaluable tool that can be used to develop innovative therapeutic approaches to poorly differentiated carcinomas in a more physiological context than using xenografts of human cell lines in immunocompromised mice.
AB - Background: Poorly differentiated and anaplastic thyroid carcinomas have a rather poor prognosis. The development of relevant model systems to unravel in vitro and in vivo the molecular mechanisms governing the resistance of these tumors to therapy, as well as to test novel drug combinations, is a clear priority for thyroid-focused research. Methods: Several novel cell lines were established from tumors developed by mice engineered to simultaneously express a loss-of-function Pten allele and an oncogenic Kras allele. Results: Similar to most poorly differentiated thyroid tumors, these cell lines are characterized by simultaneous activation of the PI3K and MAPK pathways, by the presence of wild-type, functional p53, and by the severe downregulation of thyroid differentiation markers, including sodium-iodide symporter (NIS). Further, they display a highly glycolytic phenotype. They can be grafted to syngeneic, immunocompetent hosts, and easily metastasize to the lungs. Conclusions: These mouse cell lines are a novel and invaluable tool that can be used to develop innovative therapeutic approaches to poorly differentiated carcinomas in a more physiological context than using xenografts of human cell lines in immunocompromised mice.
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U2 - 10.1089/thy.2011.0030
DO - 10.1089/thy.2011.0030
M3 - Article
C2 - 21767142
AN - SCOPUS:80052431779
SN - 1050-7256
VL - 21
SP - 1001
EP - 1007
JO - Thyroid
JF - Thyroid
IS - 9
ER -