Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

’Switched-Off’ genes put first chink in colon cell’s anti-tumor armor

15.03.2004


Johns Hopkins Kimmel Cancer Center scientists have identified a switched-off family of genes that may prove to be a significant and early dent in a colon cell’s anti-cancer armor. The inactivated genes, called SFRPs - for secreted frizzled-related protein - put the brake on a pathway of cell-growth genes that is an early step en route to cancer. Because the way SFRP genes are altered-through the attachment of so-called methyl groups-is reversible, the findings, reported in the March 14 advance online edition of Nature Genetics, also suggest potential anti-cancer value in green tea and other compounds that affect methylation. "SFRP could be a great target for preventing cancer," says Stephen Baylin, M.D., Ludwig Professor of Oncology and director for basic research at the Johns Hopkins Kimmel Cancer Center. A cancer cell stops the SFRP gene’s brake on cell growth by attaching a methyl group to a specific portion of the gene in a process called hypermethylation. Green tea and other compounds are thought to block enzymes that control methylation.



SFRP genes encode proteins that, when secreted on the cell’s surface, stop a chain reaction of cell growth directed by the WNT gene. WNT stands for "wingless type," which, along with SFRP genes, gets its name from characteristics of fruit flies with mutations in these genes. The WNT gene pathway has long been linked to colon cancer by scientists at the Kimmel Cancer Center and elsewhere.

"Previously, we thought that mutations downstream of the WNT gene were enough to trigger the cell to stay alive, keep growing and develop into a tumor. Our key finding is that the cell also may need to shut off SFRP genes to become cancerous," says Baylin. When Baylin’s team put SFRPs back into colon cancer cells with inactivated SFRP genes and mutations in the WNT pathway, the cells stopped growing uncontrollably and died.


The research team also found that inactivation of SFRP genes occurs in the earliest form of lesion, called an atypical crypt foci (earlier than polyps or cancer). Approximately 5 percent of these lesions become colon cancers. "The colon cancer process may start by shutting off SFRP genes, which allows the WNT pathway to stay on, and these colon cells grow into atypical crypt foci," Baylin explains. "Then, some of these early lesions may acquire mutations in the WNT pathway that push the cell into growth overdrive, failure to die properly, and development into polyps and, finally, cancer."

In addition to studying natural compounds, the scientists will be investigating the prevention properties of aspirin, non-steroidal anti-inflammatory drugs, and other drugs that block methylation to determine their effect on SFRP genes.


This research was funded by the National Institute of Environmental Health Services.

Other participants in the research are Hiromu Suzuki, D.Neil Watkins, Kam-Wing Jair, Kornel E. Schuebel, Yoshimitsu Akiyama, Bin Yang, and James G. Herman from the Johns Hopkins Kimmel Cancer Center; Sanford D. Markowitz from the Howard Hughes Medical Institute and Case Western Reserve University, Teresa P. Pretlow and Wei-Dong Chen from Case Western Reserve, Manon van Engeland from the University of Maastricht, the Netherlands, Minoru Toyota, Takashi Tokino and Kohzoh Imai from Sapporo Medical University, and Yuji Hinoda of the Yamaguchi University School of Medicine, Japan.

The license to the MSP technique used in this research belong to OncoMethylome. Drs. Baylin and Herman serve as consultants to OncoMethylome and are entitled to royalties from any commercial use of this procedure. The terms of this arrangement are being managed by the Johns Hopkins University according to its conflict of interest policies.

Vanessa Wasta | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>