Chromosomal complications
The paper:
B.A. Weaver et al., "Aneuploidy acts both oncogenically and as a tumor suppressor," Cancer Cell, 11:25–36. (Cited in 70 papers)
The finding:
Beth Ann Weaver, a cell biologist at the University of Wisconsin–Madison, showed that mice with lower levels of centromere protein E (CENP-E), a motor protein that sorts chromosomes during mitosis, had higher rates of abnormal chromosome numbers, or aneuploidy. CENP-E–deficient mice also had more spleen and lung tumors but, surprisingly, had fewer liver tumors.
The controversy:
Weaver's group claimed that aneuploidy was the sole culprit in altered tumor formation rates, but CENP-E might have other effects, too, says Robert Benezra of Memorial Sloan-Kettering Cancer Center. "You can never be sure that you are only inducing aneuploidy," he says. The Mayo Clinic's Jan van Deursen agrees: "The claim that this is the best model for aneuploidy...
The look back:
The findings spurred van Deursen and others to reanalyze older studies for a link between tumor suppression and aneuploidy. For example, data from New York Medical College's Wei Dai indicated that aneuploidy also suppressed cancer of the small intestine (PNAS, 102:4365–70, 2005).
The step forward:
Weaver's lab is currently testing the hypothesis that lower rates of aneuploidy drive cancer, while higher rates cause cell death and therefore suppress cancer.
Percentage of mice with cancer | ||
Cocktail | Spleen tumor | Liver tumor |
Wild type: | 0% | 14% |
CENP-E deficient: | 10% | 7% |