In vitro models of thyroid cancer.
The well defined multiple steps and alternative pathways of thyroid follicular cell neoplasia in vivo provide a theoretically ideal basis for modelling the process of epithelial tumorigenesis in vitro. Much progress has already been made in studying the earliest stages. Pure cultures of normal human follicular cells representative of the differentiation and proliferative characteristics of the intact gland can be readily prepared and genetically manipulated with retroviral vectors, permitting direct testing of the causal role of oncogenes identified from analyses of clinical samples. Such studies have provided the clearest proof to date in a human system that ras mutation is both necessary and sufficient for induction of a benign epithelial neoplasm. The contrasting effects of ret activation promise to provide a model for studying the molecular basis for the divergent behaviour of papillary and follicular tumours derived from the same normal cell. For biochemical studies requiring larger cell numbers, conditionally immortalized normal cells have shown promising results, although instability of differentiation is still a problem. Spontaneously immortalized rat cells have also proved useful for this purpose, despite their uncertain relationship to in vivo states. The major challenge now is to overcome the poor in vitro growth of thyroid cancer cells to permit meaningful reconstruction of the later stages of tumorigenesis.
Wynford-Thomas
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Department of Pathology, University of Wales College of Medicine, Cardiff.
D002471:Cell Transformation, Neoplastic; D029721:Drosophila Proteins; D011905:Genes, ras; D006801:Humans; D008954:Models, Biological; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D013539:Simian virus 40 / Q000235:genetics; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila