Scientists have discovered one way the p53 gene stops colon cancer cells. The team identified a miRNA, miR-34a, that participates in p53’s ability to kill cells likely to become malignant because of damaged genes in their nuclei.
Researchers at McKusick-Nathans Institute of Genetic Medicine suspected that p53 activates miRNAs because a number of studies have demonstrated that they are frequently abnormal in cancer cells.
To test their idea, the team first chemically damaged the DNA of two sets of colon cancer cells, one missing p53 and the other containing healthy p53. They then looked for any of the 500 known human miRNAs that are activated only in cells containing p53. They found that the miR-34a gene is turned on by p53. The experiments also showed that p53 binds directly to the genetic material near miR-34a to promote its activation.
Concluding that p53 controls miR-34a, they next teamed up with investigators at John Hopkins' department of medicine to put miR-34a into colon cancer cells. It killed cells that contained p53, but fewer were killed in cells lacking p53.
The researchers also examined pancreatic cancer cells known to contain damaged or missing p53. They found that those cells had limited or zero miR-34a. Their report will be published in the June 8 issue of Molecular Cell.