Dong and his colleagues examined the role of TOPK. This enzyme is not very active in normal tissues, but it is quite active in cancerous cells taken from blood, breast, prostate and colorectal tumors, among others. The onset of cancer could trigger the permanent turning-on of TOPK. One piece of evidence for this is that while TOPK is similar to MEK in structure, TOPK has features that suggest it is easier to keep turned on all the time.

The team performed several experiments to determine whether high TOPK activity could lead to cancer.

• When they engineered mouse skin cells to produce excessive amounts of the enzyme and then injected the cells into other mice, those mice developed tumors. Control mice had none.

• After they had silenced the gene for TOPK in human colorectal cancer cells, growth of the cells was significantly slowed compared to control colorectal cancer cells.

• The researchers also found that TOPK and a related enzyme (not MEK) activated each other in growing human colorectal cancer cells.

Taken together, these and other findings suggested that TOPK is, in effect, the key cancer-causing member of the network for which researchers have been searching, Dong said. Also, the fact that TOPK seems active mainly in cancer cells--not normal ones--means it could make a good target for chemotherapy.

How TOPK gets turned on is not known, but it appears to happen as a result of abnormal activity in cells that stems from genetic mutations in certain well-known genes. Such genes, called oncogenes, generally dont cause any trouble until mutations occur in them.

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Contact: David Ruth
druth@umn.edu
612-624-1690
University of Minnesota
31-Jul-2007