Short chromosomes put cancer cells in forced rest

Apr 25, 2007

A Johns Hopkins team has stopped in its tracks a form of blood cancer in mice by engineering and inactivating an enzyme, telomerase, thereby shortening the ends of chromosomes, called telomeres.

"Normally, when telomeres get critically short, the cell commits suicide as a means of protecting the body," says Carol Greider, Ph.D., the Daniel Nathans chair of molecular biology and genetics at Johns Hopkins. Her study, appearing online this month at Cancer Cell, uncovers an alternate response where cells simply - and permanently - stop growing, a process known as senescence.

In an unusual set of experiments, the research team first mated mice with nonoperating telomerase to mice carrying a mutation that predisposed them to Burkitt’s lymphoma, a rare but aggressive cancer of white blood cells. Telomerase helps maintain the caps or ends of chromosomes called telomeres, which shrink each time a cell divides and eventually - when the chromosomes get too short - force the cell to essentially commit suicide. Such cell death is natural, and when it fails to happen, the result may be unbridled cell growth, or cancer.

The first generation pups born to these mice contained no telomerase and very long telomeres. These mice all developed lymphomas by the time they were 7 months old. The researchers then continued breeding the mice to see what would happen in later generations. By the fifth generation, the researchers discovered that the mice had short telomeres and stopped developing lymphomas.

When the researchers blocked the suicide machinery in these fifth-generation mice, they were very surprised to find that the mice still remained cancer free.

"We were confused as to what was going on; we thought for sure that blocking the cells’ ability to commit suicide would lead to the cancer’s returning," says Greider. A closer look showed microtumors in the mice’s lymph nodes that had begun the road to cancer, but stopped, falling instead into a state of senescence.

"They don’t die, they don’t divide, they just sit there in permanent rest," says Greider.
Greider, who won the Lasker Award in 2006 for her discovery of telomerase, says further study of the road to senescence should suggest new ways of preventing or treating cancer by interfering safely with telomerase and the cell-suicide system.

Source: Johns Hopkins Medical Institutions

Explore further: New disease mechanism discovered in lymphoma

add to favorites email to friend print save as pdf

Related Stories

Partial reversal of aging achieved in mice

Nov 29, 2010

(PhysOrg.com) -- Harvard scientists at Dana-Farber Cancer Institute say they have for the first time partially reversed age-related degeneration in mice, resulting in new growth of the brain and testes, improved ...

Recommended for you

New disease mechanism discovered in lymphoma

15 minutes ago

Programmed cell death is a mechanism that causes defective and potentially harmful cells to destroy themselves. It serves a number of purposes in the body, including the prevention of malignant tumor growth. ...

Researcher to cancer: 'Resistance will be futile'

7 hours ago

Turning the tables, Katherine Borden at the University of Montreal's Institute for Research in Immunology and Cancer (IRIC) has evoked Star Trek's Borg in her fight against the disease. "Cancer cells rapidly ...

How does prostate cancer form?

9 hours ago

Prostate cancer affects more than 23,000 men this year in the USA however the individual genes that initiate prostate cancer formation are poorly understood. Finding an enzyme that regulates this process ...

Low risk of malignancy for small complex adnexal masses

16 hours ago

(HealthDay)—For older women with small complex adnexal masses, the overall risk of malignancy is low, according to a study published in the December issue of the American Journal of Obstetrics & Gynecology.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.