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Science 4 June 1993:
Vol. 260. no. 5113, pp. 1524 - 1527
DOI: 10.1126/science.8502998
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Articles

Science, Vol 260, Issue 5113, 1524-1527
Copyright © 1993 by American Association for the Advancement of Science

articles

Predisposition to neoplastic transformation caused by gene replacement of H-ras1

RE Finney and JM Bishop

George Williams Hooper Foundation, University of California, San Francisco 94143.

Homologous recombination was used to introduce a nominally transforming mutation into an endogenous H-ras1 gene in Rat1 fibroblasts. Although both the mutant and the remaining normal allele were expressed equally, the heterozygous cells were not neoplastically transformed. Instead, spontaneously transformed cells arose from the heterozygotes at a low frequency, and the majority of these cells had amplified the mutant allele. Thus, the activated H-ras1 allele was not by itself dominant over the normal allele but predisposed cells to transformation by independent events, such as amplification of the mutant allele.


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