Biology Reference
In-Depth Information
Chapter 14
Centrosome Regulation and
Breast Cancer
Zeina Kais and Jeffrey D. Parvin
Abstract Chromosomal instability and aneuploidy are commonly observed in breast
tumor cells. Loss of function of the breast- and ovarian-specific tumor suppressor gene,
BRCA1, results in supernumerary centrosomes that are likely to contribute to the
genetic instability and tumorigenesis in breast cancer cells. Other DNA repair proteins
also contribute to the regulation of the centrosome along with several oncogenic and
tumor suppressor proteins. A number of centrosome regulators that are known to be
involved in breast cancer will be discussed with a focused discussion of BRCA1 and its
ubiquitin ligase activity in the regulation of centrosome number.
14.1 Centrosome Abnormalities and Breast Cancer
Centrosome abnormalities are a major cause of genomic instability resulting in
aneuploidy that is commonly seen in tumors (Brinkley and Goepfert
1998
). Many
tumors, including breast tumors, have centrosome abnormalities characterized by
centrosome amplifications, more than two centrosomes per cell, and centrosomal
hypertrophy (Carroll et al.
1999
; Lingle et al.
1998
). Supernumerary centrosomes
can promote the formation of multipolar spindles that may ultimately cluster into a
pseudo-bipolar mitotic spindle during anaphase. This will lead to the formation of
a defective kinetochore-microtubule attachment that results in the missegregation
of chromosomes that will ultimately facilitate the formation of malignant tumors
(Ganem et al.
2009
). Centrosome abnormalities in breast cancer are mostly due to
Z. Kais
J. D. Parvin (
&
)
Department of Biomedical Informatics,
Ohio State University Comprehensive Cancer Center,
Columbus OH 43210, USA
e-mail: Jeffrey.Parvin@osumc.edu
