Suppressing p53 Inhibitor Delays Cancer

Cancer researchers have shown that an approach to cancer treatment based on disrupting the activity of the p53 (a tumor suppressor) inhibitor Mdm2 is effective in preventing the development of tumors without causing premature aging.

In its normal form, p53 acts to stop cell division whenever it senses that a cell's DNA is damaged, thus giving the cell a chance to repair the DNA before its errors are duplicated and passed on to daughter cells. In normal cells p53 is usually inactive, bound to the protein Mdm2, which prevents its action and promotes its degradation. However, when mutated, it loses its protective function; this allows mutations to accumulate in other genes and leads to more than 50 % of all human cancers, including cancers of the colon, breast, lung, bladder, brain, and liver.

Investigators at the University of Wisconsin (Madison, USA) worked with a line of Mdm-2 hypomorphic mice that express less Mdm2 than do normal mice. These mice display elevated levels of p53 activity. Results reported in the January 1, 2006, edition of Genes & Development revealed that a decrease as small as 20% in Mdm2 expression effectively prevented tumor formation without leading to premature aging.

Senior author Dr. Mary Ellen Perry, professor of oncology at the University of Wisconsin explained, "Many people develop cancer at a young age due to increased expression of Mdm2. The possibility that inhibitors of Mdm2 could delay cancer in such people without causing detrimental side effects is bolstered by our demonstration that mice expressing 30-80% the normal level of Mdm2 develop fewer tumors than wild type mice, yet age normally.”