Biology Reference
In-Depth Information
levels correlate with poorer outcomes. Hence, further work is needed to understand
the mechanisms underlying RHAMM overexpression in MM.
15.9 Aurora-A Kinase
The Aurora protein kinases, comprising Aurora-A, Aurora-B, and Aurora-C, are a
family of serine-threonine kinases that regulate many processes during cell
division (Vader and Lens
2008
). Aurora-A is recognized to play an important role
in centrosome maturation, centrosome separation, and bipolar spindle assembly
(Carmena et al.
2009
; Carmena and Earnshaw
2003
; Dutertre et al.
2002
).
During centrosome maturation, several proteins accumulate at the centrosome,
resulting in growth of the pericentriolar material (PCM) and enhanced centrosomal
microtubule nucleation activity. Aurora-A participates in this process by recruiting
pericentriolar material (PCM) proteins including centrosomin, LATS2, NDEL1,
and TACC (Mori et al.
2007
; Abe et al.
2006
; Toji et al.
2004
; Hannak et al.
2001
).
Following maturation, the centrosomes migrate to opposite poles of the bipolar
mitotic spindle in late G2; Aurora-A is also necessary for this process of centro-
some separation, as seen by abnormal monopolar spindle formation when Aurora-
A is inhibited in vitro (Glover et al.
1995
; Liu and Aurora
2006
).
The role of Aurora-A kinase in oncogenesis is well-documented. The Aurora-A
gene, AURKA, is located on chromosome 20q13, an amplification hotspot in many
tumors (Staaf et al.
2010
; Tsukamoto et al.
2008
; Scotto et al.
2008
). Aurora-A
genomic amplification has been identified in several tumor types including breast,
colon, ovarian, and prostate cancers (Zhou et al.
1998
; Sakakura et al.
2001
;
Bischoff et al.
1998
). Overexpression of Aurora-A leads to tumorigenesis and
centrosomal amplification in vitro (Zhou et al.
1998
; Meraldi et al.
2002
).
Several studies have examined Aurora-A expression in MM (Chng et al.
2008
;
Hose et al.
2009
; Dutta-Simmons et al.
2009
; Gorgun et al.
2010
). We and other
investigators have found that Aurora-A expression correlates with the CI (Chng
et al.
2008
; Hose et al.
2009
). Given its known role in centrosome amplification
(Zhou et al.
1998
), it seems likely that Aurora-A contributes to centrosome
amplification in MM as well.
15.10 Postulated Mechanisms of Centrosome Amplification
in Multiple Myeloma with Immunoglobulin
Translocations
One postulated mechanism for centrosome amplification in MM with immunoglobulin
translocations is the disruption of genomic loci encoding proteins with centrosome-
related functions as a consequence of such translocations (Maxwell and Pilarski
2005
).
Also, other genomic aberrations such as chromosome 13q deletions may be present
