This project will employ fluorescent imaging technology and biochemistry to investigate kinetic parameters and nuclear organization in epithelial cells of the rat mammary glands that are refractory to chemical carcinogens.
Our aim will be accomplished by (1) defining and comparing the cell kinetics of the proliferative compartment in carcinogen sensitive mammary glands of virgin rats with mammary glands of animals made resistant to carcinogens by hormone treatment, 2) defining the topology and identifying the stages of the cell cycle of cells in the refractory glands and (3) characterizing nuclear domains and nuclear matrix protein patterns in mammary epithelial cells in the susceptible, resistant and malignant states.
Our specific aims are to identify and characterize the proliferative compartment in the mammary gland of mature virgin and hormone treated rats and to determine the changes in the kinetics of proliferation after MNU treatment, and to identify structural changes in nuclear domains and characterize proteins of the nuclear matrix that may be specifically expressed in the mature virgin mammary glands and glands of animals made refractory to carcinogens after hormone treatment. The nuclear matrix proteins will also b analyzed in carcinogen-induced intraductal proliferations and in mammary adenocarcinoma. Antibodies will be made to nuclear matrix proteins which are unique to mammary epithelial cells of the resistant gland and to nuclear matrix proteins unique to adenocarcinoma cells. The antibodies will be used to characterize the topology of the cells of the resistant state and to follow the distribution and fate of resistant cells and adenocarcinoma cells.
| Medina, Daniel; Kittrell, Frances; Hill, Jamal et al. (2009) Prevention of tumorigenesis in p53-null mammary epithelium by rexinoid bexarotene, tyrosine kinase inhibitor gefitinib, and celecoxib. Cancer Prev Res (Phila) 2:168-74 |
| Medina, D; Kittrell, F S; Tsimelzon, A et al. (2007) Inhibition of mammary tumorigenesis by estrogen and progesterone in genetically engineered mice. Ernst Schering Found Symp Proc :109-26 |
| Caulin, Carlos; Nguyen, Thao; Lang, Gene A et al. (2007) An inducible mouse model for skin cancer reveals distinct roles for gain- and loss-of-function p53 mutations. J Clin Invest 117:1893-901 |
| Goepfert, Thea M; Moreno-Smith, Myrthala; Edwards, David G et al. (2007) Loss of chromosomal integrity drives rat mammary tumorigenesis. Int J Cancer 120:985-94 |
| Rajkumar, Lakshmanaswamy; Kittrell, Frances S; Guzman, Raphael C et al. (2007) Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models. Breast Cancer Res 9:R12 |
| Ginger, Melanie R; Shore, Amy N; Contreras, Alejandro et al. (2006) A noncoding RNA is a potential marker of cell fate during mammary gland development. Proc Natl Acad Sci U S A 103:5781-6 |
| Sharp, Z Dave; Mancini, Maureen G; Hinojos, Cruz A et al. (2006) Estrogen-receptor-alpha exchange and chromatin dynamics are ligand- and domain-dependent. J Cell Sci 119:4101-16 |
| Medina, Daniel (2005) Mammary developmental fate and breast cancer risk. Endocr Relat Cancer 12:483-95 |
| Ginger, Melanie R; Rosen, Jeffrey M (2003) Pregnancy-induced changes in cell-fate in the mammary gland. Breast Cancer Res 5:192-7 |
| Stenoien, D L; Sen, S; Mancini, M A et al. (2003) Dynamic association of a tumor amplified kinase, Aurora-A, with the centrosome and mitotic spindle. Cell Motil Cytoskeleton 55:134-46 |
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