'Switched-off' genes put first chink in colon cell's anti-t...( Johns Hopkins Kimmel Cancer Center scie...),Health

Johns Hopkins Kimmel Cancer Center scientists have identified a switched-off family of genes that may prove to be a significant and early dent in a colon cell's anti-cancer armor. The inactivated genes, called SFRPs - for secreted frizzled-related protein - put the brake on a pathway of cell-growth genes that is an early step en route to cancer. Because the way SFRP genes are altered-through the attachment of so-called methyl groups-is reversible, the findings, reported in the March 14 advance online edition of Nature Genetics, also suggest potential anti-cancer value in green tea and other compounds that affect methylation. "SFRP could be a great target for preventing cancer," says Stephen Baylin, M.D., Ludwig Professor of Oncology and director for basic research at the Johns Hopkins Kimmel Cancer Center. A cancer cell stops the SFRP gene's brake on cell growth by attaching a methyl group to a specific portion of the gene in a process called hypermethylation. Green tea and other compounds are thought to block enzymes that control methylation.

SFRP genes encode proteins that, when secreted on the cell's surface, stop a chain reaction of cell growth directed by the WNT gene. WNT stands for "wingless type," which, along with SFRP genes, gets its name from characteristics of fruit flies with mutations in these genes. The WNT gene pathway has long been linked to colon cancer by scientists at the Kimmel Cancer Center and elsewhere.

"Previously, we thought that mutations downstream of the WNT gene were enough to trigger the cell to stay alive, keep growing and develop into a tumor. Our key finding is that the cell also may need to shut off SFRP genes to become cancerous," says Baylin. When Baylin's team put SFRPs back into colon cancer cells with inactivated SFRP genes and mutations in the WNT pathway, the cells stopped growing uncontrollably and died.

The research team also found that inactivation of SFRP genes occurs in t
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Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
14-Mar-2004

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