Keener Insight into p53 Gene

During the past decade, scientists have discovered increasingly important information about how the p53 tumor suppressor gene is either missing or mutated in a majority of human cancers.

Extensive research at The University of Texas M. D. Anderson Cancer Center is de-veloping ways to replace or correct the abnormal gene, thereby realizing the potential for using gene therapy for some types of cancer.

Dr. Guillermina Lozano's laboratory studies are among those explaining the intricacies of the p53 protein.

"Nobody really knows how p53 decides whether to simply stop the cell from growing or to program the cell to kill itself," says Dr. Lozano, professor of molecular genetics at M. D. Anderson and holder of the Anise J. Sorrell Professorship.

Through her research, Dr. Lozano is finding answers that eventually should help expand targeted p53 gene therapies. So far, she has demonstrated a relationship between p53 and another gene, MDM2. Studies in mice indicate that when a cell has normal p53, it provides a delicate switching system to activate MDM2. In response, MDM2 stops the suppressing action of p53. It appears the cell needs MDM2 to progress past the embryo stage, but an over-expression also can cause proliferation typical of cancer cells.

Dr. Lozano says her team is trying to ascertain if every normal cell makes a little bit of p53 to assure there are no mistakes in a new cell. Development of new mouse models will allow extension of MDM2 research.

Although her research is very basic, Dr. Lozano says the information gained should be applicable to any tumor containing a p53 mutation. The studies illustrate the importance of detecting p53 mutations and explaining the exact nature of its flaws. She hopes to design methods to make p53 immune to MDM2, thereby creating specialized p53 genes that will destroy cancer cells.

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©2006 Texas Medical Center

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