Biology Reference
In-Depth Information
Chapter 12
Disruption of Centrosome Duplication
Control and Induction of Mitotic
Instability by the High-Risk Human
Papillomavirus Oncoproteins E6 and E7
Nina Korzeniewski and Stefan Duensing
Abstract Centrosome abnormalities and genomic instability are hallmarks of
major human malignancies and have been implicated in malignant progression as
well as therapy resistance. Since the etiology of most cancers is complex and
incompletely understood, it is vital to utilize tumors which are caused by limited
oncogenic stimuli to explore causes and consequences of centrosome aberrations
in cancer cells. High-risk HPV-associated neoplasms are suitable model systems
since only two viral oncoproteins, E6 and E7, are consistently overexpressed in
HPV-associated cancers, for example, of the uterine cervix. HPV-16 E6 and E7
have been instrumental in a number of ways to better understand centrosome
aberrations in cancer. Using these two oncoproteins, it has been shown that
centrosome overduplication and centrosome accumulation are fundamentally
different processes but can co-exist in a tumor. In this chapter we highlight the
importance of HPV oncoproteins as tools to dissect basic cellular processes in
human cancer and to provide a basis for novel translational approaches to prevent
and treat cancer.
12.1 Introduction
The concept that centrosome abnormalities, genomic instability, and cancer are
intimately linked biological events was postulated over 100 years ago by Theodor
Boveri (Boveri
2008
). Experimentally proving Boveri's hypothesis has been a
N. Korzeniewski
S. Duensing (
&
)
Section of Molecular Urooncology, Department of Urology,
University of Heidelberg, School of Medicine, Im Neuenheimer Feld 517,
69120 Heidelberg, Germany
e-mail: stefan.duensing@med.uni-heidelberg.de
