Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell-cycle triggers might be cancer drug targets

20.08.2004


Cyclin D proteins not required for development of tissues, as previously believed

In an experiment that appears to refute current theory, Dana-Farber Cancer Institute scientists have found that removing three key proteins believed essential to cell division and growth had little impact on normal tissue development of a mouse embryo. These same proteins, when overly active, have been linked to cancer cell proliferation.

With one significant exception, the absence of proteins called cyclin D1, D2, and D3 seemed to have no deleterious effect on development of the tissues and organs of laboratory mouse embryos. "D-type cyclins" are molecules that sense growth signals from the cell’s environment and, when appropriate, switch on cell division and growth. But when the system is faulty, the cyclins over-respond to the growth signals and can cause cancerous growth. The discovery that these proteins aren’t indispensable lends encouragement to an idea that blocking overactive cyclins could halt the growth of cancer.



In the Aug. 20 issue of Cell, lead author Katarzyna Kozar, MD, and senior author Peter Sicinski, MD, PhD, report on developing the first mouse embryos to date in which all three D-type cyclins were absent or "knocked out." It had been thought that at least one cyclin was required for an embryo to be viable and its tissues to form normally. Yet the "triple-knockout" mouse embryos followed a normal course of cell division and proliferation until as late as 13.5 days, when most tissues and organs are already formed. A typical mouse pregnancy last 18 days.

(In a companion paper in Cell, researchers from Spain report similar findings involving protein kinases called CDK4 and CDK6, which are molecular partners of the D-cyclins. Embryonic mice with both CDK molecules knocked out had normal tissue development as well.)

The unexpectedly viable embryos contradict theory and previous laboratory experiments. The only abnormality in the triple knockout mice was a deficiency of blood-forming cells, causing them to be pale and anemic, and was ultimately fatal. But the Dana-Farber researchers can’t yet say if this would create problems for an anti-cyclin cancer therapy in patients. "It’s not known whether D cyclins are required for blood cell generation in adults," said Sicinski. "We are addressing this in ongoing experiments."

The blood system issue aside, the results remove a major theoretical objection to developing drugs that would inhibit, or block, overactivity of cyclin D proteins, according to the study’s authors. Excess cyclin D production has been seen in tumors of the breast, head and neck and stomach, and in some blood cancers.

The main function of the D cyclins is a linking one. They respond to signals outside the cell and turn the cell-cycle machinery on when needed, enabling the cell to adjust to changes in environment. How this process is carried out in the mouse embryos with no D-type cyclins is a puzzle, says Sicinski who is also an associate professor at Harvard Medical School. "There must be alternative mechanisms that allow the cell to respond to the environment when the D-type cyclins are missing," he speculates.

But the blood-forming cells may lack such an alternative pathway, said Sicinski, and it is highly likely that cancer cells don’t, making them vulnerable to future drugs aimed at D-cyclins, or their partners, the CDK kinases.

In the Cell report, the researchers say they attempted to induce cancer in cells taken from embryos lacking the cyclins, and they remained stubbornly normal. By contrast, cells that contained the cyclins were easily made cancerous by the insertion of cancer-causing oncogenes.

That was what the scientists had hoped they would see, based on experiments reported by Sicinski in 1995 showing that mice lacking cyclin D1 had very little breast tissue and, when crossed with cancer-prone mice, had offspring that were largely protected against breast cancer.

It was those and other findings that raised the prospect of cancer therapy using drugs to block D1 and other cyclins. "Now we think it should be safe to target the cyclins with drugs that would be designed specifically to inhibit them," Sicinski says.

Bill Schaller | EurekAlert!
Further information:
http://www.dfci.harvard.edu

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>