The second is that the researchers developed a "mutant" protein that stops EZH2 from being phosphorylated, and they say this molecule might provide the basis for either a small-molecule drug or a gene therapy treatment, Hung says. Indeed, in their study, the research team used the agent to reduce tumor growth in a mouse model of human breast cancer. "We believe that identifying small molecules that could switch between the phosphorylated and nonphosphorylated EZH2 form may provide a screening strategy for cancer treatment," he says.
Finally, the study demonstrates the power of researching what is known as "epigenetics" molecular mechanisms in cancer - the notion that genes and their protein products do not have to be mutated for the disease to develop. In this field of study, researchers look at how beneficial genes/proteins may be silenced by molecules that help handle DNA.
For example, one area of active investigation is the power that histones exert on gene expression. Histones are nature's way of physically controlling unwieldy "naked" DNA by compacting it. But scientists now know that histones themselves can be modified by phosphorylation, as well as through another process known as methylation, in which one atom on a biological molecule is replaced by a different set of chemicals. Histone methylation, in particular, is now regarded as a strong modifier of genetic activity, and can work to either activate or silence gene expression.
The M. D. Anderson researchers conclude that Akt regulates the ability of EZH2 to silence genes that are needed to protect against cancer development. When Akt is activated, it phosphorylates EZH2, making it break free from a particular histone known as H3. If it is not bound to H3, EZH2 cannot methylate H3, thus
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Contact: Nancy Jensen
nwjensen@mdanderson.org
713-794-1584
University of Texas M. D. Anderson Cancer Center
13-Oct-2005