Research with Prominent Academic and Industry Scientists
Published in The Journal Molecular and Cellular Biology
CAMBRIDGE, Mass., July 29 /PRNewswire-FirstCall/ -- A new discovery about
how the extracellular environment affects the regulation of gene expression
may have important implications in the ways doctors understand and treat
diseases like atherosclerosis, psoriasis, stroke and cancer. The study, which
was published in the August issue of the journal Molecular and Cellular
Biology (vol. 22, no. 16), advances the basic understanding of the signaling
pathways and gene expression changes that allow a coordinated regulation of
angiogenesis and inflammation by endothelial cells.
(Photo: http://www.newscom.com/cgi-bin/prnh/19990824/BIOLOGO )
The study was conducted by a team of scientists from academia and
industry. Filippo Giancotti, M.D., Ph.D., of Memorial Sloan-Kettering Cancer
Center was the senior author. Research teams at Biogen (Nasdaq: BGEN) and
CuraGen Corporation (Nasdaq: CRGN) collaborated with the Memorial Sloan-
Kettering team.
The authors examined the effect that the extracellular environment can
have on cells, and found that the protein fibronectin (found in the
extracellular matrix) is capable of specifically controlling expression of
genes which play a pivotal role in inflammation and angiogenesis. The
scientists have identified the intracellular mechanism involved and
demonstrated in vivo its importance for angiogenesis.
The study authors used GeneCalling(R), a genome-wide method of mRNA
profiling, to further understand the process by which endothelial cells adhere
to extracellular matrix proteins fibronectin and laminin. GeneCalling is a
patented gene expression technology developed by CuraGen Corporation.
Adhesion of endothelial cells to extracellular matrix proteins occurs through
engagement of a family of cell surface receptors known collectively as
integrins, and results in the subsequent activation of a complex program of
gene expression. Integrins have multiple adhesive and signaling functions
that may play a crucial role in angiogenesis and inflammation. The authors
found that attachment of human endothelial cells to extracellular matrix
proteins, in particular fibronectin, can provide very potent regulation of
gene expression. Many of the identified genes are considered highly
significant to angiogenesis and inflammation.
One of the most novel aspects of this work is the discovery of how
integrin-related signaling pathways, which have been extensively studied by
Dr. Giancotti, are involved in the regulation of a program of gene expression
important for angiogenesis and inflammation. Adhesion of endothelial cells to
fibronectin through the alpha5beta1 integrin, but not to laminin through the
alpha2beta1 integrin, activates gene transcription. This occurs through a
signaling pathway requiring several well-known intracellular proteins,
including Ras, phosphatidylinositol 3-kinase, and members of the Rho family.
Commenting on the group's findings, Biogen's Victor E. Koteliansky, M.D.
Ph.D., and Dr. Antonin de Fougerolles, Ph.D., said, "We are very pleased to
have been able to collaborate on this work with Dr. Giancotti and his
colleagues at Memorial Sloan-Kettering, as well as with researchers from
CuraGen Corporation. We are excited to further our understanding of how the
environment in which cells reside affects their biological function. These
interactions occur largely through integrin proteins, in which Biogen has had
a long-standing interest. We have now successfully described on a
comprehensive basis how extracellular matrix can affect endothelial cell
function and dissected the molecular signaling pathways responsible. This
study takes us another step closer to finding new and improved ways to
regulate angiogenesis and inflammation."
Angiogenesis is the formation of new blood vessels from pre-existing ones.
It requires endothelial cells to migrate, proliferate and assemble into tubes
that regulate selective transport of white blood cells and solutes. Several
observations suggest that angiogenesis and inflammation proceed in a
coordinated fashion and sustain one another during wound healing and tissue
repair, as well as in cancer and a variety of chronic inflammatory diseases.
About Biogen
Biogen, Inc., winner of the U.S. National Medal of Technology, is a
biotechnology company principally engaged in discovering and developing drugs
for human healthcare through genetic engineering. Headquartered in Cambridge,
MA, the Company's revenues are generated from U.S. and European sales of
AVONEX(R) (Interferon beta-1a) for treatment of relapsing forms of multiple
sclerosis, (please see full prescribing information at
http://www.avonex.com.), and from the worldwide sales by licensees of a number
of products, including alpha interferon and hepatitis B vaccines and
diagnostic products. Biogen's research and development activities are focused
on novel products to treat inflammatory and autoimmune diseases, neurological
diseases, cancer, fibrosis, and congestive heart failure. The Company
maintains active clinical research programs in protein therapeutics, small
molecules, genomics and gene therapy. For copies of press releases and
additional information about the Company, please consult Biogen's homepage on
the World Wide Web at http://www.biogen.com.
About Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center is the world's oldest and largest
institution devoted to prevention, patient care, research and education in
cancer. Their scientists and clinicians generate innovative approaches to
better understand, diagnose and treat cancer. Memorial Sloan-Kettering's
specialists are leaders in biomedical research and in translating the latest
research to advance the standard of cancer care worldwide.
About CuraGen
CuraGen Corporation (Nasdaq: CRGN) is a genomics-based pharmaceutical
company. CuraGen's integrated, functional genomic technologies and Internet-
based bioinformatic systems are designed to generate comprehensive information
about genes, human genetic variations, gene expression, protein interactions,
protein pathways, and potential drugs that affect these pathways. The Company
is applying its industrialized genomic technologies, informatics, and
validation technologies to develop protein, antibody, and small molecule
therapeutics to treat obesity and diabetes, cancer, inflammatory diseases, and
central nervous system (CNS) disorders. CuraGen is headquartered in New
Haven, CT. Additional information is available at http://www.curagen.com.
SOURCE Biogen, Inc.
 back to top
Related links:
http://www.curagen.com
http://www.biogen.com
Photo Notes:
NewsCom:
http://www.newscom.com/cgi-bin/prnh/19990824/BIOLOGO
AP Archive: http://photoarchive.ap.org
PRN Photo Desk, 888-776-6555 or 212-782-2840
Company News On-Call:
http://www.prnewswire.com/gh/cnoc/comp/101550.html
CONTACT:
media, Tim Hunt, Director, Public Affairs,
+1-617-679-4996, or investors, Christina Dillon, Manager,
Investor Relations, +1-617-679-2521, both of Biogen, Inc.
|
