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Screening for genes linked to p53 and cell suicide
Researchers use microarrays to compare the activity of 5,730 genes in tumor cells
By Bijal P. Trivedi

The p53 protein plays a critical role in triggering suicide in a cell when DNA has been damaged beyond repair. Researchers have developed a screening process to identify other proteins that assist p53 in bringing about cell death. These new molecules could serve as drug targets for cancers that are resistant to p53.

One of p53's functions is to prevent mutated cells from dividing. In many types of cancer, the p53 gene is missing or disabled, and cells with damaged DNA continue to thrive and divide.

Researchers at Texas A&M University Health Science Center, in College Station, compared the activity of genes in two types of cancer cells: those that are sensitive to p53-induced death and those that resist p53-induced death. Using DNA microarray technology, the researchers compared the activity of 5,730 genes in the two types of cells.

The expression of 480 genes was either increased or decreased by two-fold among the sample cells. One gene that was twice as active in p53-sensitive cells was proline oxidase. The proline oxidase gene produces a chemical associated with the death of both p53-sensitive and p-53-resistant cells. In lung cancer cells without p53, proline oxidase was able to substitute for p53 and trigger cell suicide.

"We conclude that a proline oxidase molecule localizes to the mitochondria and is capable of inducing apoptosis [cell death] in a transformed human cell line," the researchers write in the Proceedings of the National Academy of Sciences.

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Maxwell, S.A. et al. Differential gene expression in p53 apoptosis-resistant vs. apoptosis-sensitive tumor lines. Proc Natl Acad Sci USA 97, 13009-13014 (November 21, 2000).

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