. Regulation of cell cycle depends on the scheduled expression of a class of proteins termed cyclins, and the interaction of these proteins with cyclin-dependent kinases (Cdk) and cyclin-dependent kinase-inhibitor (Cki) proteins. Derangement in cell cycle regulatory proteins clearly contributes to the uncontrolled cell growth that is characteristic of cancer. Thus, these proteins are implicated as causal factors in the development of cancer. Information from several studies, support the hypothesis that altered expression of a G1 phase cyclin, Cyclin E, is a common and highly relevant occurrence in breast cancer. Preliminary studies indicate that Cyclin E is aberrantly expressed in breast cancer tissue: 1) it is present at higher levels in cancer cells than benign cells in the same patient; 2) in some tumors, it appears to be independent of proliferation; and 3) high levels of expression are associated with tumors of higher grade and poor prognosis. The plan is to test tumors from women enrolled in the ongoing study, """"""""Factors That Affect Survival of Young Cancer Patients,"""""""" and evaluate Cyclin E and the cell cycle inhibitors (p27 and p21) expression in invasive breast cancer specimens, using immunocytochemical and flow cytometric assays. The results are expected to be combined with the extensive epidemiological, clinical, and histopathological, tumor marker, and flow cytometric cell cycle data currently being collected as part of the larger study. The data are expected to provide important new information of the cyclins in the development of breast cancer and, in this large population, will allow determination of whether alterations of Cyclin E and cell cycle inhibitor protein expression are predictors of recurrence or death in breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA071735-01A1
Application #
2010148
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1997-06-20
Project End
2000-04-30
Budget Start
1997-06-20
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Lund, Mary Jo; Trivers, Katrina F; Porter, Peggy L et al. (2009) Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat 113:357-70
Trivers, Katrina F; Lund, Mary Jo; Porter, Peggy L et al. (2009) The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control 20:1071-82
Porter, Peggy L; Lund, Mary Jo; Lin, Ming Gang et al. (2004) Racial differences in the expression of cell cycle-regulatory proteins in breast carcinoma. Cancer 100:2533-42
Li, C I; Malone, K E; Porter, P L et al. (2003) Epidemiologic and molecular risk factors for contralateral breast cancer among young women. Br J Cancer 89:513-8