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 Speed data for the brain’s navigation system
06.12.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science 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: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>