CENTROSOME HYPERTROPHY IN HUMAN BREAST TUMORS

Project: Research project

Project Details

Description

DESCRIPTION: (adapted from the investigator's abstract) The centrosome
functions in maintenance of cell polarity and in progression through the
cell cycle by determining the number, polarity, and organization of
interphase and mitotic spindle microtubules. Defects in centrosome
organization and function have profound consequences for the cell, including
the characteristic loss of cell polarlity and chromosomal segregation
abnormalities seen in many cancer cells. Cell cycle checkpoints regulating
centrosome duplication are believed to operate under the influence of p53.

In preliminary studies, they have performed a careful examination of
centrosomes in human breast tumors to determine if centrosome abnormalities
occur in these cells. The preliminary studies have revealed striking and
characteristic changes in several centrosome properties in breast tumor
cells including: excess accumulation of key centrosomal proteins,
supernumerary centrioles, and inappropriate phosphorylation status of
centrosome proteins. In addition, they have developed a novel microtubule
nucleation assay to assess breast tumor cell centrosome function. Their
preliminary studies further demonstrate that breast tumor cells show
specific functional centrosome abnormalities characterized by inappropriate
numbers of MTOCs that nucleate large microtubule asters. They, therefore,
propose to: 1) determine the cell cycle control mechanism for centrosome
duplication in normal breast epithelial and breast tumor derived cell lines,
2) to determine the functional relationship between alterations in
centrosome structure and the loss of cell polarity and increase in
chromosomal segregation abnormalities seen in breast carcinomas, and 3) to
systematically and quantitatively characterize molecular and structural
markers for centrosome abnormalities in human breast tissues from
proliferating and nonproliferating fibrocystic disease, LCIS, DCIS, and
invasive ductal and lobular carcinomas.

The proposed studies represent a novel approach to understanding the
mechanism of loss of both cell polarity and the increased propensity toward
chromosomal segregation abnormalities seen in many carcinoma cells, and
these studies may provide new targets useful in the development of novel
clinical interventions.
StatusFinished
Effective start/end date1/1/986/30/08

ASJC

  • Medicine(all)