Biology Reference
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Fig. 10.3 Loss of p53 and centrosome amplification. Cells in any given populations and even
under the optimal growth conditions are subjected to physiological and genotoxic stresses,
resulting in the cell cycle arrest in a p53-independent manner. In cells with functional p53, p53 is
upregulated by various mechanisms during the arrest. p53 then upregulates p21, which effectively
inhibits CDK2. Without the activity of CDK2, newly duplicated centrosomes cannot undergo
reduplication. In contrast, in cells lacking functional p53, p21 cannot be upregulated during the
arrest, and if the active CDK2 is available, newly duplicated centrosomes undergo reduplication,
resulting in centrosome amplification. Once the stress-causing problems are resolved, those cells
will resume cell cycling with amplified centrosomes
cyclin E. The careful examination of bladder cancer specimens has revealed that
this is indeed the case (Kawamura et al.
2004
). This study shows that the occur-
rence of centrosome amplification parallels with increased frequencies of p53
mutation and cyclin E overexpression, and the multivariate analysis of the bladder
cancer specimens in respect to status of p53, cyclin E expression and chromosome
instability/centrosome amplification shows that there is a strong association
between concomitant occurrence of p53 mutation and cyclin E overexpression and
chromosome instability/centrosome amplification, but p53 mutation or cyclin E
overexpression alone is not significantly associated with chromosome instability/
centrosome amplification. Because cyclin E overexpression is frequent in many
types of tumors (Keyomarsi and Herliczek
1997
), the univariate analysis of p53
and chromosome instability/centrosome amplification tends to give a positive
association. However, if cyclin E overexpression is a rare event in the tumor types
under examination, the association between p53 mutation and chromosome
instability/centrosome amplification will likely be weak. In support, it has been
