March 2, 2007

Ha-ras Goes It Alone In Bladder Cancer

Cancer occurs when a particular cell or group of cells begins to grow in an uncontrolled manner. Such uncontrolled growth can be caused by an increase in the activity of proteins that promote cell growth, by a decrease in the activity of proteins that inhibit cell growth, or a combination of these two. In most tumors of the bladder, the activity of the protein Ha-ras, which promotes cell growth, is increased. However, it has been unclear whether increased Ha-ras activity is sufficient to cause bladder cancer, or even if it is necessary for bladder cancer to develop.

In a study appearing online in advance of publication in the February print issue of the Journal of Clinical Investigation, Xue-Ru Wu and colleagues from New York University show that low levels of increased Ha-ras activity are insufficient to induce bladder tumors in mice. Surprisingly, combining this low level increase in Ha-ras activity with loss of a protein that inhibits cell growth (Ink4a/Arf) did not induce bladder tumors. However, doubling the activity of Ha-ras rapidly induced the growth of bladder tumors in all the mice analyzed, indicating that the extent of Ha-ras increased activity influences whether or not it induces the development of bladder tumors. The authors therefore suggest that targeting this molecule, as well as signaling molecules downstream of it, might provide a new avenue of research for the development of agents to treat bladder cancer in humans.

TITLE: Hyperactivation of Ha-ras oncogene, but not Ink4a/Arf deficiency, triggers bladder tumorigenesis

Xue-Ru Wu
New York University School of Medicine, Manhattan Veterans Affairs Medical Center, New York, New York, USA.


JCI table of contents: January 25, 2006

Contact: Karen Honey
Journal of Clinical Investigation

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