Download the ezh2 oncogene induces the inactivation of tumor

Nature publishes a collaborative work of the Epigenetics Group of CNIO that
demonstrates a cooperation between oncogenes and epigenetics in the road to
tumorigenesis
THE EZH2 ONCOGENE INDUCES THE INACTIVATION OF
TUMOR SUPPRESSOR GENES
Madrid, Dicember 15th 2005.- The EZH2 oncogene induces the inactivation of tumor
suppressor genes, according to the last findings published in Nature by Dr Manel
Esteller, director of the Cancer Epigenetics Group at the CNIO and Dr François Fuks,
head of the Molecular Virology Laboratory at the Free University of Brussels.
“It is the first time”, explained Manel Esteller, “that there is a formal demonstration of a
connection between an oncogenic factor and an epigenetic factor leading to cancer
development". In this work the researchers found that the EZH2 protein act as a
"molecular magnet" to attract aberrant DNA methylation to the genome. This malignant
and excessive DNA methylation, mediated by the enzymes DNA methyltransferases,
provokes the inactivation of genes that in normal cells protect against the development
of tumoral processes.
The EZH2 oncogene is the first example of a protein with the capacity to transform a
normal cell in a cancer cells due only to its epigenetic activity: the ability to methylate
histones, proteins that embrace DNA and regulate its fuction; a function that it already
altered in cancer cells, as the group of Manel Esteller demonstrated this year in Nature
Genetics.
“These findings”, emphasized Manel Esteller, “demonstrates the essential role of
Epigenetics in cancer. EZH2 causes aberrant methylation of histones, but at the same
time aberrant methylation of the DNA, rendering many tumor suppressor genes in an
inactive form."
The implications of these discoveries are critical for the understanding of the origin of
cancer and the future development of better cancer treatments. In this regard, the
EZH2 oncogene is overexpressed and undergo different chromosomal aberrations in
many tumor types, such as in prostate cancer. "These alterations", add Manel Esteller,
"could induce the silencing of critical genes such as WNT1. Interestingly, there are
compounds that can restore the expression of these genes by changing their DNA and
histone methylation patterns. One of these drugs is already being tested for an
hematological premalignant disease, myelodisplastic syndrome. Finally, it is worth to
mention that EZH2 is also involved in the right development of the human embryo and
our findings could have an impact in pathologies where genetic malformations are
present".
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