JHU Med 2002-43 (cancer)

[Dennis O'Shea]

Johns Hopkins Medical Institutions
Office of Communications and Public Affairs
Media Contact: Vanessa Wasta
410-955-1287
E-mail: wastava@jhmi.edu
May 9, 2002

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EMBARGOED FOR RELEASE ON MONDAY, MAY 13, AT 5 P.M. EDT
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KEY POWERHOUSE ENZYME LINKED TO CANCER DEVELOPMENT

Scientists at the Johns Hopkins Kimmel Cancer Center have discovered that 
an enzyme found in a tumor cell's energy center has a special relationship 
with a gene that controls cancer cell growth and death. Their findings, 
published in the May 14 issue of the Proceedings of the National Academy of 
Sciences, may offer a road map to anti-cancer therapies designed to 
manipulate the genetic pathway that switches the enzyme on and off.

The enzyme PRDX3 inhabits mitochondria, the tiny organelles that provide 
energy to cells and a meeting ground for regulation of cell life and 
death.  "What this research suggests is that we might be able to shut down 
tumors by learning how to control this enzyme," says Chi Dang, M.D., Ph.D., 
director of the division of hematology and professor of medicine, cell 
biology, pathology and oncology.

Proteins made by the PRDX3 gene, known to be overexpressed in breast 
cancer, chew up or reduce oxidants called peroxides entering the 
cell.  Hopkins investigators used a scanning method to "skip" through 
pieces of the PRDX3 gene and precisely pinpoint areas where certain 
proteins bind to it, acting like ignition switches to increase 
expression.  The investigators found that a key ignition switch controlling 
activation of PRDX3 is a well-known cell growth-promoting cancer gene 
called c-MYC.

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 they shut down PRDX3, turning off its 
ability to make its enzyme, the mouse tumors stopped growing.  When they 
turned it back on, 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 
doesn't work," explains Dr. Dang.  "In this case, we've 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," says Dr. Dang.

This research was funded by the National Cancer Institute, National 
Institutes of Health.

Other participants in this research were Diane Wonsey and Karen Zeller of 
Johns Hopkins.

Diane R. Wonsey, Karen I. Zeller, and Chi V. Dang, "The c-MYC target gene 
PRDX3 is required for mitochondrial homeostasis and neoplastic 
transformation," Proceedings of the National Academy of Sciences, May 2002, 
Vol. 99, Issue 10: pp. 6649-6654.

On the Web:
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: 
www.hopkinskimmelcancercenter.org

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