Biology Reference
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contain extra centrosomes in about 60 % of their somatic cells. Although many of
the fly cells with supernumerary centrosomes initially form multipolar spindles,
they ultimately cluster into bipolar arrays, resulting in only slightly increased CIN
levels. Nevertheless, larval brain cells of these animals can generate metastatic
tumors when transplanted into the abdomens of wild-type hosts (Basto et al.
2008
).
Similar to flies, mice overexpressing the centrosomal protein ninein-like
(NINL) show centrosome amplification as detected in mouse embryonic fibroblasts
from the transgenic animals and develop tumors of breast, ovary, and testicles at
10-15 months of age (Shao et al.
2010
). Whether or not extra centrosomes are
clustered into bipolar mitoses in this system was not examined. Although NINL
overexpression will certainly have additional effects other than centrosome
amplification these data nevertheless indicate a role of supernumerary centrosomes
in tumorigenesis in mammals as well.
The ability to cluster supernumerary centrosomes into a bipolar mitotic spindle
array is not a specific trait of tumor cells. For example, during physiological
hepatocyte polyploidization, primary binuclear hepatocytes—which naturally
contain four centrosomes in the G
2
phase—efficiently cluster pairs of centrosomes
at opposite spindle poles, leading to the generation of mononuclear 4n progeny
(Guidotti et al.
2003
). Recent data confirm that polyploid mouse hepatocytes in
most cases reorganize their spindles into a bipolar mitotic array from an inter-
mediate multipolar state. This process was associated with lagging chromosomes
in 25-50 % of tetraploid hepatocytes undergoing bipolar anaphase and resulted in
a high rate of aneuploidy (Duncan et al.
2010
). Interestingly, however, a small
percentage of tetraploid mouse hepatocytes underwent successful tripolar divi-
sions, producing viable offspring. Moreover, during liver regeneration in mice,
which is associated with excessive polyploidization, about 20 % of hepatocytes
missegregate one or more chromosomes at each mitosis (Putkey et al.
2002
),
possibly also a consequence of centrosomal clustering. Furthermore, several
studies showed that both non-transformed Drosophila melanogaster (D. melano-
gaster) neuroblasts and diverse types of human cells that have been manipulated to
contain supernumerary centrosomes by either PLK4 overexpression or treatment
with cytochalasin D to inhibit cytokinesis, can cluster multiple centrosomes into a
bipolar spindle array both in vitro and in vivo (Ganem et al.
2009
; Basto et al.
2008
; Quintyne et al.
2005
; Kwon et al.
2008
; Yang et al.
2008
).
Collectively, it seems that not only cancer cells but also non-transformed cell
types can cluster supernumerary centrosomes into bipolar mitotic spindles. Initial
evidence implicates supernumerary centrosomes and centrosomal clustering in
tumorigenesis in flies. However, data generated in mouse hepatocytes show that
neither centrosome amplification nor centrosome clustering or multipolar cell
division with subsequent aneuploidy necessarily leads to malignant transformation
in mammals. From those data it can also be concluded that multipolar divisions are
not universally lethal. However, as these experiments have been performed using
polyploid hepatocytes, surviving multipolar divisions might well be a peculiarity
of polyploid cells which better tolerate the loss of multiple chromosomes.
