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My name is Jason Carroll.
I'm a group leader at Cancer Research UK,
at the Cambridge Research Institute at the University of Cambridge.
What I'm going to talk about today is some work that's come from ChIP-on-chip experiments
over the last couple of years, where we've mapped
oestrogen receptor binding sites on a genome-wide level,
and we've been mining these binding sites to learn about
underlying properties and features of
oestrogen receptor transcription in breast cancer cells.
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We are interested in the role of the oestrogen receptor in breast cancer.
We know from the genomic revolution about seven or eight years ago
that when researchers performed gene expression profiling in primary breast cancers
and looked for patterns within the gene expression profiles,
they found that
primary breast cancers could be subcategorised into various subtypes.
This included basal tumours that were driven by ERBB2,
but by far the largest category of tumours were those that were called 'luminal tumours'.
These were tumours that expressed
the oestrogen receptor, and tended to express oestrogen receptor target genes.
This shows the large percentage of breast cancers that are
represented by luminal or ER-positive breast cancers (n.b., the abbreviation ER uses the US spelling 'estrogen').
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On a molecular level, this is probably the most simplified version of how oestrogen and
oestrogen receptor can generate
gene transcription events, that can culminate in cell division in breast cancer cells.
We know that oestrogen is a steroid.
It can diffuse into breast cancer cells and it
binds to an intracellular protein, namely oestrogen receptor.
Oestrogen receptor can dimerize and
these homodimers can bind to the promoters of target genes.
These target genes are subsequently transcribed by the transcription machinery,
and the gene transcription events that culminate from these pathways represent
the gene expression profiles that you see in luminal or ER-positive breast cancers.
With the knowledge that oestrogen receptor
bound to promoters of specific target genes,
we could use technology and
technological advances (such as chromatin immunoprecipitations) to map
oestrogen receptor binding sites, and to guess about particular
co-factors or proteins that might be on the promoters of these target genes.
