Lymphocytes from lymph nodes obtained at mastectomy in breast cancer patients have been fused with murine nonproducer myeloma cells to obtain human-mouse hybridoma cultures that synthesize human monoclonal antibodies. To date, 52 hybridoma cultures synthesizing either human IgG or human IgM have been obtained from lymph nodes of 13 patients. Ig production was stable in many of these cloned cult...

The tumor suppressor gene p53 is frequently mutated in human breast cancer and is a marker for poor prognosis and resistance to chemotherapy. Transplantation of p53 null mouse mammary epithelium into syngeneic wild-type mice leads to normal mammary gland development followed by spontaneous mammary tumors that recapitulate many of the phenotypic, molecular and genetic features of human breast ca...

Epithelial cells isolated from the mammary glands of virgin Sprague-Dawley rats and treated with 7,12-dimethylbenz[a] anthracene (DMBA) acquire an indefinite life span and anchorage-independent (AI) growth and form carcinomas in athymic nu/nu mice. Epithelial cells separated from fibroblasts and lipocytes by density-gradient centrifugation after collagenase digestion of the fat pads are grown i...

Proliferation and differentiation of mammary epithelial cells are governed by hormonal stimuli, cell-cell, and cell-matrix interactions. Terminal differentiation of mammary epithelial cells depends upon the action of the lactogenic hormones, insulin, glucocorticoids, and prolactin that enable them to synthesize and secrete milk proteins. These differentiated cells are polarized and carry out ve...

Transduction of mitogenic signals in cells can be mediated by molecules derived from the synthesis and breakdown of the major membrane phospholipid, phosphotidylcholine. Studies were performed on human mammary epithelial cells in culture to understand the impact of malignant transformation and progression on membrane phospholipid metabolism. In the model system used here, phosphocholine levels ...

Experiments were conducted to redirect mouse Embryonic Stem (ES) cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this....

We have studied the generation of reactive oxygen species during the metabolism of a carcinogen, benzo[a]pyrene, by human mammary epithelial cells. We have quantitated the production of one type of oxidative DNA damage, thymine glycols, by using a monoclonal antibody specific to this base modification. Thymine glycols were produced in DNA in a dose-dependent manner after exposure of human mamma...

Any epithelial portion of a normal mouse mammary gland can reproduce an entire functional gland when transplanted into an epithelium-free mammary fat pad. Mouse mammary hyperplasias and tumors are clonal dominant populations and probably represent the progeny of a single transformed cell. Our study provides evidence that single multipotent stem cells positioned throughout the mature fully devel...

Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78 as regulators of stem cell behavior in isolated fetal and adult mammary epithelial cells. We develop a CRIPTO antagonist that promotes differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By...

Synthetic rexinoids effectively suppress both estrogen receptor-positive and estrogen receptor-negative mammary tumors in animal models, which makes them prime candidates for a novel class of cancer-preventive agents. When used in combination with chemotherapy for non-small-cell lung cancer, the rexinoid bexarotene was most effective for patients who developed hypertriglyceridemia as a side eff...