Investigators Discover that Mutated p53 Induces Tumor Formation and Metastasis

GEN News Highlights

The University of Texas M. D. Anderson Cancer Center scientists found that a mutated form of p53 is stabilized by Mdm2, an inhibitor of normal p53 activity, thus increasing tumor growth and metastasis. This research also lends insight into a potential pitfall of using Mdm2 inhibitors for cancer therapy.

The research team demonstrated that a particular mutated form of p53 prevalent in human cancers is inherently unstable in normal tissues but can become stable in some cells. This stabilization of mutated p53 is produced by the p53-antaogonist Mdm2. The investigators also found that transgenic mice engineered to harbor such mutations showed enhanced tumor formation and metastasis compared with littermates lacking p53.

The researchers point out that targeted drug therapies aimed at activating p53 tumor suppressor activity via the disruption of the normal Mdm2/wild-type-p53 interaction could also succeed in stabilizing mutant p53 and fail in preventing tumor metastasis.

“Our data are both exciting and sobering; we must classify tumors with respect to p53-mutation status prior to treatment,” emphasizes one of the authors Guillermina Lozano, Ph.D., professor and chair in the department of cancer genetics at M. D. Anderson Cancer Center.

The study is published in the May 15 issue of Genes & Development.

Source : http://www.genengnews.com/