The long term objective of this work is to determine the sequential cellular changes following irradiation leading to mammary tumor formation. Experiments using the cell dissociation (CD) and epithelial focus (EF) assays over the last project period have provided information on cellular changes based on in vivo and in vitro growth parameters. Cell lines were also developed which have been used to study neoplastic progression. The proposed experiments are designed to take advantage of the unique opportunities made possible with these model systems to extend these studies to examine the role of chromosome alterations, oncogenes and growth factors in mammary tumor development. Cytogenetic and molecular biologic techniques will be used to more fully characterize tumors and the altered cellular phenotypes observed to precede mammary tumor development. These studies will use tumors as well as tissues, primary cells, and cell lines obtained from the CD and EF assays to: (1) determine whether specific chromosomal alterations are associated with mouse mammary tumors; (2) determine whether specific chromosomal alterations are associated with phenotypic changes observed during tumorigenesis; (3) determine whether specific oncogenes are associated with mammary tumors; (4) determine whether specific oncogenes are associated with specific altered growth phenotypes during neoplastic progression; and (5) examine biochemical alterations associated with the altered growth phenotypes.
| Fabre, Kristin M; Ramaiah, Lila; Dregalla, Ryan C et al. (2011) Murine Prkdc polymorphisms impact DNA-PKcs function. Radiat Res 175:493-500 |
| Williams, Eli S; Klingler, Rebekah; Ponnaiya, Brian et al. (2009) Telomere dysfunction and DNA-PKcs deficiency: characterization and consequence. Cancer Res 69:2100-7 |
| Carsten, Ronald E; Bachand, Annette M; Bailey, Susan M et al. (2008) Resveratrol reduces radiation-induced chromosome aberration frequencies in mouse bone marrow cells. Radiat Res 169:633-8 |
| Hagelstrom, R T; Askin, K F; Williams, A J et al. (2008) DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals. Oncogene 27:6761-9 |
| Williams, Eli S; Stap, Jan; Essers, Jeroen et al. (2007) DNA double-strand breaks are not sufficient to initiate recruitment of TRF2. Nat Genet 39:696-8;author reply 698-9 |
| Bailey, Susan M; Murnane, John P (2006) Telomeres, chromosome instability and cancer. Nucleic Acids Res 34:2408-17 |
| Bailey, S M; Goodwin, E H; Cornforth, M N (2004) Strand-specific fluorescence in situ hybridization: the CO-FISH family. Cytogenet Genome Res 107:14-7 |
| Bailey, Susan M; Brenneman, Mark A; Halbrook, James et al. (2004) The kinase activity of DNA-PK is required to protect mammalian telomeres. DNA Repair (Amst) 3:225-33 |
| Bailey, Susan M; Brenneman, Mark A; Goodwin, Edwin H (2004) Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. Nucleic Acids Res 32:3743-51 |
| Bailey, Susan M; Cornforth, Michael N; Ullrich, Robert L et al. (2004) Dysfunctional mammalian telomeres join with DNA double-strand breaks. DNA Repair (Amst) 3:349-57 |
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