title: Establishment and characterization of cell lines from a novel mouse model of poorly differentiated thyroid carcinoma: powerful tools for basic and preclinical research.
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.
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Mariavittoria
authors.initials: M
authors.lastname: Dima
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Miller
authors.forename: Valeria Gabriela
authors.initials: VG
authors.lastname: Antico-Arciuch
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Cristofano
mesh_terms: D018263:Adenocarcinoma, Follicular; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D058539:Phosphatidylinositol 3-Kinase; D020928:Mitogen-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)