Scientists in Australia have discovered how female steroid hormones can
make dramatic changes to the genetic material in breast cells.
Scientists in Australia have
discovered how female steroid hormones can make dramatic changes to the genetic
material in breast cells, changes that could potentially lead to breast cancer.
The study, published recently in
the journal Cell Reports, was conducted by researchers from the
Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.
Here, they created a roadmap of
the epigenomes of different breast cell types, and determined how the
epigenomes changed in response to ovarian hormones such as progesterone. The
epigenome is a series of chemical tags that modify DNA, controlling which genes
are switched on and off.
“We found the epigenome was very
sensitive to hormonal regulation,” said Professor Jane Visvader, a senior
author on the study. “This reveals another way in which female hormones can
influence breast cancer risk – by altering the epigenome through modifications
in DNA tags.”
The epigenome is where the DNA
and the environment intersect, communicating signals from the outside world to
the DNA. The epigenome doesn’t alter the genetic code, but is a layer of
proteins that sits ‘on top’ of the DNA and provides instructions on whether DNA
should be read and ‘switched on’ to produce proteins.
The research team found that
pregnancy hormones activate a molecule called EZH2, which is an important
modifier of the epigenome.
“We found that hormones including
progesterone activate EZH2 to modify the epigenome, leading to global changes
in the expression of a huge number of genes,” Visvader said.
“In normal tissue, EZH2 is
essential for the development of breast tissue including ducts and
milk-producing cells, and for maintaining the activity of breast stem cells and
their daughter progenitor cells.
However, life-long exposure to
hormones could lead to breast tumor initiation through increased levels of EZH2
and the changes that it orchestrates in the epigenome,” she explained.
Breast cancer is the most common
cause of cancer in women, accounting for almost 30 percent of all cancers
affecting women. High levels of EZH2 are a marker of poor prognosis in breast
cancer and have been frequently observed in basal-like breast cancers, the most
aggressive types of breast cancer.
“The link between progesterone,
EZH2 and the epigenome, could be crucially important in the very early stages
of breast cancer development,” she said.
Professor Geoff Lindeman, another
senior author on the study, said there were decades of evidence linking hormone
exposure with breast cancer, but the hormones’ influence on the epigenome was
not known.
“Our discovery points to a role
for hormone-induced changes in the epigenome in the early stages of breast
cancer initiation, and could lead to new therapeutics for treating breast
cancer,” Lindeman said.
“Inhibitors against EZH2 are
being developed by others, but it will be several years before we know the
outcome of these on cancer.”
The article can be found at: Pal B et al. (2013) Global Changes
in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2.
Source: WEHI;
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