RT Journal Article
SR Electronic
T1 Activation of ras oncogenes preceding the onset of neoplasia
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1101
OP 1104
DO 10.1126/science.2188364
VO 248
IS 4959
A1 Kumar, R
A1 Sukumar, S
A1 Barbacid, M
YR 1990
UL http://science.sciencemag.org/content/248/4959/1101.abstract
AB 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.