The cyclooxygenase (COX)-2 gene encodes an inducible prostaglandin synthase enzyme that is overexpressed in adenocarcinomas and other tumors. Deletion of the murine Cox-2 gene in Min mice reduced the incidence of intestinal tumors, suggesting that it is required for tumorigenesis. However, it is not known if overexpression of Cox-2 is sufficient to induce tumorigenic transformation. We have der...

Mammary carcinogenesis induced through expression of activated Raf was investigated using a model in which retroviral vectors were infused into the central ducts of rat mammary glands. This model allows efficient expression of experimental proteins in a small fraction of endogenous mammary epithelial cells in situ. We previously reported that Raf is the dominant oncogenic signaling pathway from...

Milk lipids originate by secretion of triglyceride-rich cytoplasmic lipid droplets (CLDs) from mammary epithelial cells. Adipophilin (ADPH)/Plin2, a member of the perilipin family of CLD binding proteins, is hypothesized to regulate CLD production in these cells during differentiation of the mammary gland into a secretory organ. We tested this hypothesis by comparing CLD accumulation in differe...

Although the neuropilins were characterized as semaphorin receptors that regulate axon guidance, they also function as vascular endothelial growth factor (VEGF) receptors and contribute to the development of other tissues. Here, we assessed the role of NRP2 in mouse mammary gland development based on our observation that NRP2 is expressed preferentially in the terminal end buds of developing gl...

Female rats of ten different inbred strains were tested for their suscep tibility to 7, 12-dimethylbenz|a|anthracene (DMBA)-induced mammary adenocarcinogenesis. Five of these strains (OM. NSD, \VI. LEWIS, BUFF) were demonstrated to be highly susceptible to DMBA exposure developing >2 continuously growing, macroscopically detectable mam mary adenocarcinomas/rat following gastric intubation with ...

In this report, we have shown that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. MiR146b expression was significantly higher in the mammary glands of pregnant and lactating mice than in virgin mice. Furthermore, miR146b levels were significantly higher in mouse mammary glands exposed to the sex hormones, estrogen and progesterone, compared with thos...

The genetically related ACI and Copenhagen (COP) rat strains display diametrically opposed susceptibilities to mammary cancer development when treated chronically with 17beta-estradiol (E2). Here, we compare the actions of E2 on cell proliferation and lobuloalveolar development in the mammary glands of female ACI and COP rats. After 12 wk of E2 treatment, the mammary glands of ACI rats exhibite...

Insulin is known to be an important regulator of milk secretion in the lactating mammary gland. Here we examine the role of insulin signaling in mammary development in pregnancy using a mouse with a floxed insulin receptor (IR) crossed with a mouse expressing Cre specifically in the mammary gland. In the mammary glands of these IR(fl/fl) Cre(+) mice, expression of IR is significantly diminished...

Osteopontin (OPN) is a secreted phosphoprotein that binds to cells via an Arg-Gly-Asp sequence and to mineralized surfaces. The protein can mediate cell adhesion and is strongly implicated in transformation and tumorigenesis. We have examined the expression pattern of OPN in mouse mammary glands at different stages of postnatal development. Whereas OPN is expressed at low-to-moderate levels in ...