Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New genetic option for thwarting cancer

18.11.2002


From ultraviolet radiation to food carcinogens, our bodies are bombarded with stuff that can make a normal cell go haywire, multiplying out of control and turning cancerous. Thanks to a set of tumor suppressor genes, however, we can defend against this daily onslaught.



Goaded into action, these genes push cells into a kind of molecular menopause, called senescence. The cells remain healthy, but they stop reproducing.

Researchers often assume that we need our tumor suppressor genes to remain disease-free; otherwise we fall prey to cancer. Indeed, in roughly half of all human tumors, the suppressor gene called p53 is defective.


Now, however, in a study reported in today’s issue of Genes and Development, University of Illinois at Chicago investigators have shown that we don’t need these genes to stop the development of cancer. Another gene can take their place.

"We found that if you knock out a single gene called Cdk4, you can still make cells cancer resistant, even if their tumor suppressor defense mechanism is deficient," said Dr. Hiroaki Kiyokawa, assistant professor of molecular genetics and a member of the UIC Cancer Center. "Cells still go into senescence."

The finding opens up a new option for cancer therapy: targeting the Cdk4 gene or the enzyme it produces.

"This is an outstanding target, particularly since so many cancer cell types and precancerous tissues have faulty tumor suppressor genes," Kiyokawa said.

According to Kiyokawa, the Cdk4 gene normally accelerates cell division through the enzyme it manufactures. He became curious about the role of Cdk4 in cancer when the scientific literature pointed to its elevated enzyme activity in melanomas, gliablastomas, breast and ovarian tumors and other cancers.

In an earlier trial, Kiyokawa and his colleagues attempted to induce skin papillomas, or tumors, in mice bred in their laboratory without the Cdk4 gene. They painted the animals’ skin with a widely used carcinogen, but virtually no tumors developed.

In the present study, the researchers set out to understand how Cdk4 inhibits tumor growth. They deleted the Cdk4 gene in mouse fibroblast cells, derived from connective tissue, and made the cells cancer prone by inactivating two tumor suppressor genes, p53 and Ink4a/Arf. The cells became senescent even when p53 or Ink4a/Arf was absent, yielding proof that Cdk4 is required for a cell to become cancerous.

Importantly, the mice that lack the Cdk4 gene appeared healthy, although they were smaller than average and sometimes developed diabetes, Kiyokawa said. That is, even without the Cdk4 gene, they developed no severe abnormalities -- an indication that future cancer therapy could target the Cdk4 gene without significantly disrupting normal cell function.

"Losing Cdk4 does not appear to be critical for the body’s normal growth pattern. Such an important function as cell division is bound to be regulated by multiple redundant pathways that can take over when Cdk4 is gone," Kiyokawa said.

In fact, Kiyokawa doesn’t think that Cdk4 is even necessary for regular cell growth.

"Normal cell division is like cruising along the highway at the legal speed limit," Kiyokawa said. "Cancerous cell division is like flooring the accelerator. The car can quickly get out of control. Driving at 55 miles an hour doesn’t require Cdk4. You need Cdk4 only if you are speeding."

Kiyokawa believes that Cdk4 mobilizes when cells hit their "mileage limit" -- the end of their proliferative life span. After completing a preprogrammed number of divisions, cells normally stop multiplying.

To stop, they need tumor suppressor genes -- or at least that’s what researchers to date have assumed. Otherwise, they keep growing, under the influence of Cdk4.

"In cancer, cells exceed their mileage limit. For that, Cdk4 is necessary," Kiyokawa said. "By eliminating Cdk4, we can force cells to stop dividing, inducing senescence, which is exactly what tumor suppressor genes normally do."

Future studies in Kiyokawa’s laboratory will focus on developing strategies to sabotage the Cdk4 gene and its growth-accelerating enzyme in cancer-prone patients.

Other researchers involved in the present study were Xianghong Zou, Dipankar Ray, Aileen Aziyu, and Konstantin Christov of UIC and Alexander Boiko and Andrei Gudkov of the Lerner Research Institute at the Cleveland Clinic Foundation.


The study was supported by the American Cancer Society

Sharon Butler | EurekAlert!
Further information:
http://www.uic.edu/com/cancer.
http://www.uic.edu/

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>