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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-06-01
    Description: 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, R -- Sukumar, S -- Barbacid, M -- 1-RO1-CA48943/CA/NCI NIH HHS/ -- N01-CO-74101/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 1;248(4959):1101-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Squibb Institute for Medical Research, Princeton, NJ 08543.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2188364" target="_blank"〉PubMed〈/a〉
    Keywords: Adenofibroma/genetics ; Animals ; Animals, Newborn ; Base Sequence ; Carcinoma/genetics ; Cell Transformation, Neoplastic/*genetics ; Estrogens/physiology ; Female ; Gene Expression Regulation, Neoplastic/*physiology ; Genes, ras/*physiology ; Mammary Glands, Animal/growth & development ; Mammary Neoplasms, Experimental/chemically induced/*genetics ; Methylnitrosourea ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; Rats ; Rats, Inbred Strains ; Sexual Maturation ; Time Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1988-04-22
    Description: These studies were set up to determine whether those oncogenes participating in the initiation of mammary carcinogenesis (for example, ras oncogenes) play a direct role in the outcome of events associated with the late stages of tumor development such as loss of hormone dependency. Mammary carcinomas induced by a single carcinogenic insult in pubescent rats was selected as an in vivo model system with direct relevance to human breast cancer. Acquisition of hormone-independent growth in these carcinogen-induced tumors was found to be independent of the activation of ras oncogenes during the early stages of carcinogenesis. In agreement with these observations, introduction of a human ras oncogene into human MCF-7 breast carcinoma cells did not abrogate their hormonal dependency for growth in vivo. These findings suggest that those events responsible for the critical stages of breast cancer development occur independently and in an uncoordinated manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sukumar, S -- Carney, W P -- Barbacid, M -- N01-CO-74101/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1988 Apr 22;240(4851):524-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Oncology Section, Basic Research Program, Frederick Cancer Research Facility, MD 21701.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3282307" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*physiopathology ; Cell Line ; Estrogens/*physiology ; Gene Expression Regulation ; *Genes, ras ; Humans ; Mammary Neoplasms, Experimental/*physiopathology ; Methylnitrosourea ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Rats ; Receptors, Estrogen/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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