title: Androgen-dependent mammary carcinogenesis in rats transgenic for the Neu proto-oncogene.
abstract: Transgenic rats were created with overexpression of the Neu proto-oncogene in the mammary gland of both sexes, yet only males developed mammary cancer in an androgen-dependent fashion. Transgenic females only developed mammary cancer if treated with androgens. These tumors were positive for androgen receptor (AR), but negative for estrogen and progesterone receptors. Extensive analysis failed to detect mutations anywhere within the neu transgene from mammary carcinomas. Established mammary carcinomas eventually escaped their dependency on androgens. Transgenic long-term gonadectomized rats did not develop mammary cancer, but Neu overexpression stimulated the growth of their mammary glands. Our results suggest crosstalk between the Neu proto-oncogene and AR signaling pathways in the growth of both the normal and cancerous mammary epithelium.
authors.affiliation: University of Wisconsin-Madison, McArdle Laboratory for Cancer Research, 53706, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Watson
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Kim
authors.forename: Kai-Shun
authors.initials: KS
authors.lastname: Chen
authors.forename: Michael N
authors.initials: MN
authors.lastname: Gould
mesh_terms: D000375:Aging; D000818:Animals; D030801:Animals, Genetically Modified; D004305:Dose-Response Relationship, Drug; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics*; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000235:genetics; D011944:Receptors, Androgen / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology* / Q000502:physiology; D013997:Time Factors
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone