Using yeasts to study cancer
A new study from the journal Nature, and summarized recently on io9.com, shows that under stressful conditions yeast cells do not faithfully segregate their chromosomes during cellular division. This produces a chromosomal condition called aneuploidy, where an aberrant number of chromosomes are found in each cell. In a normal cell, aneuploidy is an undesirable situation, as the carefully balanced number of genes normally found in the cell becomes disrupted. Yeast can be particularly hard hit by aneuploidy, as many fungi spend a significant portion of their life cycle in the haploid state, with only one copy of a given chromosome. Loss of a chromosome as the number of chromosomes becomes unstable during aneuploidy means that certain important genes will be completely lost from the genome, and would never be recovered.
The finding from the Nature article, and summarized at io9.com is that stressful situations can promote unfaithful chromosome segregation during cellular division. Researchers exposed a diploid strain of the budding yeast Saccharomyces cerevisiae to a variety of stress conditions, then measured the rate of chromosome loss formation. What the researchers found was that aneuploidy arose at high frequency to stress conditions, and that loss or gain of various chromosomes as the yeasts were stressed conferred certain advantages to those strains. For instance, yeast exposed to the drug fluconazole, a common antifungal medicine, tended to have acquired an extra copy of Chromosome VIII.
The researchers also found that exposure of yeast to very low levels of the drug radicicol (at levels insufficient to markedly slow down the growth rate) developed aneuploid colonies at a high rate, and these colonies showed resistance to radicicol and to a variety of other antifungal drugs. Aneuploidy then can give a significant growth advantage under a variety of non-optimal environmental conditions. Aneuploidy is not optimal for growth under normal conditions, and consequently mutant yeast removed from the stressful conditions reacquired a normal complement of chromosomes.
So what does this have to do with cancer? Cancerous cells are also marked by chromosomal instabilities, and aneuploidy removes some of the cell cycle blocks that are the hallmark of normal cellular division. A proper chromosomal balance keeps unchecked cellular division under control, and disruptions lead to uncontrolled growth. The problem is compounded when we try to treat cancers in the patient with chemotherapeutic drugs; these compounds put additional stresses on cells, which this research shows that they can respond by becoming resistant through additional chromosomal instability.
The summary at io9.com concludes with this statement:
The toxins in chemotherapy can kill cancer cells, the way that a fungicide can kill yeast cells, but if the chemo drugs also trigger the cancer cells to lose or gain chromosomes, the tumor may be able to adapt to the stressful environment and survive the chemotherapy. To avoid this situation and make cancer treatments more effective, further research should explore the link between stressful environments and faster adaptation.
If this stress response pathway holds true in all eukaryotic cells, we also need to be aware that the same chemo drugs will be putting pressure on normal cells in this process, which may promote additional cancer cell emergence. This gives us an additional impetus to avoid aneuploidy as we search for novel anti-cancer treatments.
Posted on February 7, 2012, in Microbes in the News, Strange but True and tagged Aneuploidy, Cancer, Saccharomyces cerevisiae, Yeast. Bookmark the permalink. Comments Off on Using yeasts to study cancer.