Braking Genes and Cancer Cell Division

February 2007 - A study by a team of physicists, mathematicians, computer scientists, and biologists from the Weizmann Institute of Science in Israel, the Sheba Medical Center and the M.D. Anderson Cancer Center in Houston, Texas, published in the online edition of Nature Genetics, has identified a number of genes involved in the mechanism that prevents uncontrolled cell division and found that aberrations are linked to certain types of cancer as well as to the relative aggressiveness of the disease.

Researchers explain that cell division is one way in which cancer cells differ from normal cells. Normal cell division is prompted by an external chemical signal from a growth factor initiating a sequence of events within the cell. Researchers mapped the network of genes activated as a result and found that some of the proteins produced caused cell division while others put brakes on the process. Researchers hope that the current study may lead to development of mechanisms to "restore the brakes" in cancer cells and halt disease progression.

The study found that after receipt of the growth factor signal, cell activity occurs in separate waves in which genes are turned on and off for different periods of time. First the activity of a few genes increases for about 20 to 40 minutes, causing cell division. However, the next four waves, from 40 to 240 minutes after the signal, primarily involve gene activity associated with the breaking mechanism, halting cell division. Researchers identified 50 genes that interfere with the first wave, producing proteins that directly attach to the cell-division genes or dismantle messenger RNA carrying instructions for cell division.

Tissues from ovarian cancer patients revealed a correlation between levels of activity in the "braking" genes, survival rates, and the aggressiveness of the disease. Researchers suggest that these findings may contribute to development of a personal genetic profile, identifying genetic defects responsible for each cancer, tailoring individual treatment plans, and helping to predict prognosis.

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