Activation of ras oncogenes preceding the onset of neoplasia

Journal Article · Fri Jun 01 04:00:00 EDT 1990 · Science (Washington, D.C.); (USA)

DOI:https://doi.org/10.1126/science.2188364· OSTI ID:6155731

Kumar, R; Barbacid, M ^[1]; Sukumar, S ^[2]

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1. Squibb Institute for Medical Research, Princeton, NJ (USA)
2. Salk Institute, La Jolla, CA (USA)

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.

• OSTI ID: 6155731
• Journal Information: Science (Washington, D.C.); (USA), Journal Name: Science (Washington, D.C.); (USA) Vol. 248:4959; ISSN SCIEA; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BODY
CARCINOGENESIS
CARCINOMAS
CELL TRANSFORMATIONS
DISEASES
ENZYMES
ESTROGENS
EXPERIMENTAL NEOPLASMS
GENES
GLANDS
HORMONES
MAMMARY GLANDS
NEOPLASMS
NITROSO COMPOUNDS
NITROSOUREAS
NUCLEOTIDYLTRANSFERASES
ONCOGENES
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
STEROID HORMONES
TRANSFERASES