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Science 1 June 1990:
Vol. 248. no. 4959, pp. 1101 - 1104
DOI: 10.1126/science.2188364
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Articles

Science, Vol 248, Issue 4959, 1101-1104
Copyright © 1990 by American Association for the Advancement of Science

articles

Activation of ras oncogenes preceding the onset of neoplasia

R Kumar, S Sukumar, and M Barbacid

Department of Molecular Biology, Squibb Institute for Medical Research, Princeton, NJ 08543.

The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes.


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