A Gene That May Block Prostate Cancer's Spread

Finding could lead to genetic therapies to treat variety of cancers

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TUESDAY, June 17, 2003 (HealthDayNews) -- Researchers have identified a gene that appears to play a key role in governing the spread of cancerous prostate cells to other parts of the body.

Experts know prostate cancer often doesn't kill -- it's the spread of those cancerous cells from the gland to other areas of the body that does. So the finding could help identify ways to control the spread of potentially deadly tumors, the University of Michigan researchers say.

Approximately 20 genes involved in the spread -- or metastasis -- of prostate cancer have already been identified. The new one -- designated RKIP, which produces the RKIP protein -- is important because it serves as a kind of traffic cop. It acts early to stop cancer cells from leaving the prostate and entering the bloodstream and wreaking havoc, says a report in the June 18 issue of the Journal of the National Cancer Institute.

"There is a metastatic cascade, in which the cells enter the blood vessels, then go into a target organ, then grow there," says study author Evan T. Keller, an assistant professor of comparative medicine and pathology at the University of Michigan Medical School.

"This gene [RKIP] works at an early stage in the cascade. If you can block that stage, you could prevent the cascade," he explains.

The researchers work with RKIP is also important because they've been able to identify a specific function of the gene, Keller says. "With all of the genes associated with metastasis, we haven't made a lot of progress in identifying their function," he adds.

The hope is the discovery will open the way for gene therapy or even drug therapy that will act on the RKIP gene and prevent the spread of cancerous prostate cells to other organs and tissues, Keller says.

The RKIP gene -- the initials stand for Raf kinase inhibitor protein, which it makes -- acts to suppress metastasis. Cancer cells that have a full quota of the RKIP gene are unlikely to metastasize. Those that have little or none of it do spread, Keller says.

The researchers spent three and a half years studying the workings of the gene, starting in a laboratory with two lines of human cancer cells -- one non-metastatic, one metastatic. The scientists first found the RKIP gene was relatively inactive in the metastatic cells.

Then they began more specific measurements. One critical test used cancer cells taken from prostate cancer patients within hours of their death, when the fragile molecules involved in RKIP activity were still present. RKIP levels in 12 samples of non-metastatic cancers were close to those of healthy cells. But no RKIP protein was found in any of the 22 samples of metastatic prostate cancer.

Then there were trials of a basic sort of gene therapy, adding the RKIP gene to cells grown in the laboratory, then to mice with prostate cancer. Adding the gene reduced metastasis in cell cultures and the animals.

Some additional proof came from the Human Genome Project. The RKIP gene is on chromosome 12, and one study done as part of the project showed that suppression of metastasis was associated with that chromosome.

Keller and his colleges are moving in several directions. One is to see whether the RKIP gene plays a role in metastasis of other cancers, such as breast, lung and liver tumors.

"And we are trying to look at the mechanism of how this gene affects what the tumor is doing," Keller says.

More information

You can learn more about prostate cancer from the National Cancer Institute or the National Library of Medicine.

SOURCES: Evan T. Keller, D.V.M, Ph.D., University of Michigan Medical School, Ann Arbor; June 18, 2003, Journal of the National Cancer Institute
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