Establishment and characterization of cell lines from a novel mouse model of poorly differentiated thyroid carcinoma

Powerful tools for basic and preclinical research

Mariavittoria Dima, Kelly A. Miller, Valeria Gabriela Antico-Arciuch, Antonio Di Cristofano

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1001-1007
Number of pages7
JournalThyroid
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2011

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Thyroid Neoplasms
Thyroid Gland
Cell Line
Alleles
Research
Differentiation Antigens
Drug Combinations
Tumor Cell Line
Phosphatidylinositol 3-Kinases
Heterografts
Neoplasms
Down-Regulation
Carcinoma
Phenotype
Lung
Therapeutics

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Establishment and characterization of cell lines from a novel mouse model of poorly differentiated thyroid carcinoma : Powerful tools for basic and preclinical research. / Dima, Mariavittoria; Miller, Kelly A.; Antico-Arciuch, Valeria Gabriela; Di Cristofano, Antonio.

In: Thyroid, Vol. 21, No. 9, 01.09.2011, p. 1001-1007.

Research output: Contribution to journalArticle

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