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Stepwise transformation of primary thyroid epithelial cells by a mutant Ha-ras oncogene: an in vitro model of tumor progression

Burns, Jorge S., Blaydes, Jeremy P., Wright, Pat A., Lemoine, Louise, Bond, Jane A., Williams, E. Dillwyn and Wynford-Thomas, D. (1992) Stepwise transformation of primary thyroid epithelial cells by a mutant Ha-ras oncogene: an in vitro model of tumor progression Molecular Carcinogenesis, 6, (2), pp. 129-139. (doi:10.1002/mc.2940060208).

Record type: Article


Activating mutations of the ras oncogene family occur at high frequency in all stages of thyroid tumorigenesis, both human and experimental. To test the causal nature of this association, and to investigate the biological role of ras mutation, we introduced a mutant c-Ha-ras gene into
normal rat thyroid follicular cells using an ecotropic retroviral vector. The major immediate effect was to greatly extend the proliferative lifespan of these cells in culture from less than 3 to more than 15 doublings, without any observable loss of growth-factor dependence or differentiated functions. This in vitro phenotype strongly supports an initiating role for ras mutation in the genesis of benign thyroid tumors (adenomas) in vivo. Spontaneous transformation was observed at low frequency on continuous culture of mutant ras-expressing cells, giving rise to fully immortalized, growth factor-independent, highly tumorigenic lines. Transformation was associated with (i) loss of responsiveness to the growth inhibitor TGF-beta 1, and (ii) greatly increased nuclear levels of p53 protein, which unexpectedly was not due to point mutation in the conserved regions of the p53-coding sequence. We postulate that these two phenomena are causally related to each other and to the transformed phenotype.

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Published date: 20 July 1992
Keywords: p53, TGF-?, tumor suppressor genes


Local EPrints ID: 150593
ISSN: 0899-1987
PURE UUID: 5ae34eb5-e8bf-45eb-b88b-3acf4cd0c1fa

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Date deposited: 16 Jun 2010 10:33
Last modified: 18 Jul 2017 12:57

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Author: Jorge S. Burns
Author: Pat A. Wright
Author: Louise Lemoine
Author: Jane A. Bond
Author: E. Dillwyn Williams
Author: D. Wynford-Thomas

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