Obesity is associated with increased risk for postmenopausal, but not premenopausal breast cancer. Recently, we reported that intact obese Zucker rats had increased susceptibility to DMBA-induced mammary tumors compared to lean Zucker rats. In the present study, we investigated whether excessive adipose tissue would promote mammary tumor induction in the absence of ovarian estrogen. Lean and ob...

One topical application of 0.02 mmole of /V-hydroxy-2fluorenylacetamide to the left thoracic glands of adult female Sprague-Dawley rats gave a 70% tumor incidence at the site. The tumors appeared 3 to 6 months after the application and were mammary adenocarcinomas. In contrast, the tumor incidence after application of N-2fluorenylacetamide was 30%, the latent period was 8 to 11 months, and the ...

The Ron receptor tyrosine kinase (macrophage stimulating 1 receptor) is overexpressed in approximately 50% of human breast cancers. Transgenic mice overexpressing Ron in the mammary epithelium [mouse mammary tumor virus driven (MMTV)-Ron expressing mice] develop mammary tumors that exhibit up-regulation of β-catenin and β-catenin target genes. β-Catenin has been shown to be a mediator of mammar...

Breast cancer is a genetically and clinically heterogeneous disease, and the contributions of different target cells and different oncogenic mutations to this heterogeneity are not well understood. Here we report that mammary tumors induced by components of the Wnt signaling pathway contain heterogeneous cell types and express early developmental markers, in contrast to tumors induced by other ...

To improve our understanding of the effects of androgens on the induction and growth of mammary tumors, the interaction of androgen on the estrogen receptor (ER) has been evaluated in the 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor. In vitro competitive experiments have shown that androgens interact on ER with a low affinity but have a good stereospecificity for C,9 steroids bearin...

High molecular weight DNAs of five tumors induced by mouse mammary tumor virus (MMTV), two mouse mammary tumors induced by a chemical carcinogen, and one human mammary tumor cell line (MCF-7) were assayed for the presence of transmissible activated transforming genes by transfection of NIH 3T3 mouse cells. DNAs of all five MMTV-induced tumors, one chemical carcinogen-induced tumor, and the huma...

To improve our understanding of the effects of androgens on the induction and growth of mammary tumors, the interaction of androgen on the estrogen receptor (ER) has been evaluated in the 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor. In vitro competitive experiments have shown that androgens interact on ER with a low affinity but have a good stereospecificity for C,9 steroids bearin...

Human diseases such as Nijmegen breakage syndrome due to mutations in the NBS1 gene result in defects in resection of double strand breaks. NBS1 functions as part of the MRN complex which functions in homologous recombination and non-homologous end joining. NBS is a rare human autosomal recessive disorder caused by hypomorphic mutations. At the ce...

Receptor Activator of NF-kappa B (RANK) pathway controls mammary gland development in mice but its role in mammary stem cell fate remains undefined. We show that constitutive RANK signaling expands luminal and basal mammary compartments including mammary stem and luminal progenitor cell pools and interferes with the generation of CD61+ and Sca1+ luminal cells and Elf5 expression. Impaired mamma...

The fibroblast growth factor-related protooncogenes, int-2 and hst/k-FGF, are within 17 kilobase pairs of one another on mouse chromosome 7 and are in the same transcriptional orientation. Approximately 70% of tumors induced in BR6 mice by mouse mammary tumor virus have proviral insertions adjacent to the int-2 gene. We find that the murine homolog of the hst/k-FGF gene can also be transcriptio...