DESCRIPTION: (Adapted from Applicant's Abstract). 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.
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