Control of Gene Expression in Tumor Cell Mito

Deregulated expression of the c-MYC transcription factor is found in a wide variety of human tumors.

Proteins made by the PRDX3 gene reduce oxidants called peroxides entering the cell. Investigators from John Hopkins University (Baltimore, MD, USA) used a method called chromatin immunoprecipitation analysis to precisely pinpoint protein binding and activation areas of the PRDX3 gene. The investigators found that the c-MYC gene was essential for activation of PRDX3. These findings were published in the May 14, 2002, issue of the Proceedings of the National Academy of Sciences.

The use of mitochondria-specific fluorescent probes also demonstrated that PRDX3 is essential for maintaining mitochondrial mass and membrane potential in transformed rat and human cells. To find out how c-MYC and PRDX3 work together, the scientists looked at different levels of PRDX3 activation in rat and human cancer cell lines where c-MYC was turned on. When PRDX3 was shut down, the mouse tumors stopped growing. When it was turned back on, the tumors grew rapidly.

"Think of PRDX3 as a light bulb and c-MYC as the light switch. If you remove the light bulb even though the switch may be on, the lamp still does not work,” explained Dr. Chi V. Dang. "In this case, we have removed the light bulb rendering the switch powerless.”

"These results show that changing PRDX3 activation can alter how tumors grow. Now, our challenge is to find out in which cancers this pathway is most important and what drugs may do the job,” said Dr. Dang.



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