RNA & Prostate Cancer

September 26, 2003

Science News

Week of Jan. 26, 2002; Vol. 161, No. 4

Cancer clue: RNA-destroying enzyme may thwart prostate-tumor growth

The size and shape of a walnut, the prostate gland is the source

of

the fluid that carries a man's sperm. It's also a source of great

concern to many men: In 2001, physicians in the United States

diagnosed nearly 200,000 cases of prostate cancer and more than

30,000 men died of the disease.

By studying families that include several men with prostate

cancer,

scientists have now identified a tumor-suppressing gene on

chromosome

1. It's unclear whether mutations in this eagerly sought gene will

ultimately explain many cases of prostate cancer, but

investigators

are optimistic that their work has revealed a novel facet of

tumor-cell biology. Also, they say, the finding could suggest new

ways of diagnosing or treating prostate cancer.

Although newly associated with prostate cancer, the gene has been

studied since the 1970s. It encodes an enzyme known as RNase L,

which

degrades RNA, a chemical relative of DNA. Linking defects in this

gene to prostate cancer is " the first example where RNA turnover

is

implicated in tumor suppression, " says H. Silverman of the

Cleveland Clinic Foundation.

Silverman has investigated RNase L for most of his career. Last

year,

he got an unexpected phone call from a group of geneticists who

had

been tracking down a hereditary prostate cancer gene on chromosome

1

since 1996. The geneticists, led by Carpten of the National

Human Genome Research Institute in Bethesda, Md., told Silverman

that

they had found inherited mutations in the gene for RNAse L in two

families plagued by prostate cancer. The researchers, including

Silverman, now reveal their findings in the February Nature

Genetics.

The most widely recognized duty of RNase L is to suppress

infections

by degrading viral and cellular RNA, but there have been hints

that

the enzyme limits tumor growth. RNase L helps damaged cells commit

suicide, which is one way the body defends itself against both

cancer

and viral infections.

" I hope people working on other types of cancer will now put [the

gene for] RNase L on the list of genes they look at, " says

Silverman.

In the new study, the men with prostate cancer had inherited

mutations in one of their two copies of the enzyme's gene. Then, a

spontaneous mutation in a prostate cell must have deactivated the

other copy, permitting the cell to avoid suicide and divide

without

limits.

Of eight families the geneticists suspected of having a prostate

cancer-causing gene on chromosome 1, only two have so far revealed

mutations in the gene for RNase L, Carpten and his colleagues

report.

They continue to look for disabling mutations in the gene in the

other families.

The gene for RNAse L is only the second gene to be identified for

hereditary prostate cancer, which makes up about 10 percent of

cases.

The first has so far accounted for only a few prostate cancer-

prone

families and is not commonly mutated in men who develop prostate

cancer without a family history of the disease (SN: 10/7/00, p.

230).

While the gene for RNase L may similarly explain just a small

fraction of prostate cancer cases, its protein could offer insight

into more-general causes of the cancer and perhaps an avenue to

treat

it. Researchers have also struggled to distinguish unthreatening

prostate tumors that grow slowly from those that quickly kill a

man.

Measuring the activity of RNase L in tumors might provide another

clue for such crucial diagnoses.

The new study is " simultaneously exciting and disappointing, " says

cancer geneticist Rebbeck of the University of

Pennsylvania

School of Medicine in Philadelphia. " It's a very interesting

finding,

but we need to find out a lot more about this gene before we

understand its role in hereditary prostate cancer or prostate

cancer

in general. "

To that end, Carpten and his colleagues plan to join geneticists

at

University in Washington, D.C., to study the gene in about

60

African-American families with a strong history of prostate

cancer.

African-American men, for reasons largely unknown, are much more

likely than men in most other ethnic groups to develop prostate

cancer and die from it.

References and Sources

References:

Carpten, J., . . . and J. Trent. 2002. Germline mutations in the

ribonuclease L gene in families showing linkage with HPC1. Nature

Genetics (February). Abstract.

Sign In

RNA & Prostate Cancer

Recommended Posts

Guest guest

Link to comment

Share on other sites

Join the conversation

Activity