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 Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>