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Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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The activated human Ha-ras oncogene was subjected to the control of the promoter region of the murine whey acidic protein (Wap) gene, which is expressed in mammary epithelial cells in response to lactogenic hormones. The Wap-ras gene was stably introduced into the mouse germ line of five transgenic mice (one male and four females). Wap-ras expression was observed in the mammary glands of lactating females in two lines derived from female founders. The tissue-directed and hormone-dependent Wap expression was conferred on the Ha-ras oncogene. The signals governing Wap expression are located within 2.5 kilobases of 5' flanking sequence. The other two lines derived from female founders did not express the chimeric gene. In the line derived from the male founder the Wap-ras gene is integrated into the Y chromosome. Expression was found in the salivary gland of male animals only. After a long latency, Wap-ras-expressing mice developed tumors. The tumors arose in tissues expressing Wap-ras - i.e., mammary or salivary glands. Compared to the corresponding nonmalignant tissues, Wap-ras expression was enhanced in the tumors.
Research Organization:
Ludwig Institute for Cancer Research, Bern, Switzerland
OSTI ID:
6179262
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:5; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CHROMOSOMES
DAYS LIVING RADIOISOTOPES
DISEASES
FOOD
GENE REGULATION
GENE REPRESSORS
GENES
GLANDS
ISOTOPES
LACTATION
LIGHT NUCLEI
MAMMALS
MAMMARY GLANDS
MAN
MATERIALS
MICE
MILK
NEOPLASMS
NUCLEI
NUCLEOPROTEINS
ODD-ODD NUCLEI
ONCOGENES
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
RODENTS
VERTEBRATES