Senescence prevents the proliferation of genomically damaged, but otherwise replication competent cells at risk of neoplastic transformation. p16INK4A (p16), an inhibitor of CDK4 and CDK6, plays a critical role in controlling cellular senescence in multiple organs. Functional inactivation of p16 by gene mutation and promoter methylation is frequently detected in human breast cancers. However, d...

The rat mammary epithelial stem cell line, Rat Mammary 25, and the dimethyl sulfoxide-resistant variant derived from it, Rama 259, when injected separately into female, virgin, athymic nude mice formed tumors which grew at approximately the same rate. When the mice were mated, the growth rate of the Rama 259 tumors increased 2.5-fold during late pregnancy and lactation, while that of the Rama 2...

Saturable, high-affinity binding sites for 3,5,3'-triiodo-u-thyronine (T3) were identified in isolated nuclei and solubilized chromatin extracts of mammary glands, spontaneous mam mary tumors, and liver from C3H/HeN mice. Receptor concen tration in whole mammary gland nuclei (254 fmol/mg DMA) was only about one-half that of mouse liver nuclei (536 fmol/ mg DNA), but in molecular weight (55,000)...

To examine the behavior of tumor cells in tumors developing directly from mammary tissue in transgenic models, we have evaluated transgenic mice expressing green fluorescent protein (GFP). Using the mouse mammary virus promoter (MMTV) to directly drive expression of GFP, we find low levels of fluorescence in the mammary and salivary glands of transgenic animals. Using MMTV-Cre or WAP-Cre in com...

R, and the frequency of induced mammary tumors. This apparent linear dose-effect relation does not hold after exposure to fission neutrons, at least from 10 to 250 rads, in single whole-body exposures. The female Sprague-Dawley rat has a relatively high spontaneous incidence of mammary tumors. However, these neoplasms appear late in life in unirradiated controls. Only 2% of 89 control rats show...

There is abundant evidence that estrogens enhance the development of mammary tumors in high-cancer strains of mice, with the possible exception of the Marsh-Buffalo strain. The inhibitory effect of testosterone in this connection is also well known. Although similar studies in species other than the mouse have yielded conflicting results, there is evidence that estrogens enhance the development...

Transgenic mice expressing the polyomavirus (PyV) middle T antigen (MT) develop multifocal mammary tumors which frequently metastasize to the lung. The potent transforming activity of PyV MT is correlated with its capacity to activate and associate with a number of signaling molecules, including the Src family tyrosine kinases, the 85-kDa Src homology 2 subunit of the phosphatidylinositol 3' (P...

DNA synthesis in mammary gland estimated by [3H]thymidine incorporation was significantly higher on the day of proestrus than on the second day of diestrus in 50-day-old female Sprague-Dawley rats. The percentage of progressive mammary tumors, tumor growth rate, and the number and the weight of tumors per tumor-bearing rat were significantly higher in the animals given a single i.v. injection o...

Many components of Wnt/beta-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli) in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cr...

Female transgenic mice that constitutively overexpress the transcription factor ATF3 in the basal epithelium of the mammary gland develop mammary carcinomas with high frequency, but only if allowed to mate and raise pups early in life. This transgenic mouse model system reproduces some features of human breast cancer in that about 20% of human breast tumor specimens exhibit overexpression of AT...