The discovery as to how exactly the genetic message of oestrogen receptor-alpha is regulated sets up a future scenario in which functional assays of this kind can be performed on sufferers, leading to a more targeted treatment.
Breast cancer has long been a prime candidate for a more focused therapy and scientists strongly believe the existence of oestrogen signalling and changes in epigenetic control in breast cancer could be a pathway that could be relatively easy to disrupt.
Oestrogen receptor activity is known to be regulated in two ways. Ligand- or steroid-dependent occurs when the receptor has to bind to a small molecule to become active.
The other approach is independent of the ligand and requires the action of another kind of molecule, like a growth factor to become active. Through this research, the scientists were able to see how the receptor was affected by the two different types of stimulation, distinguishing between them.
Scientists from the Baylor College of Medicine in Houston used high throughput microscopy that uses robots and techniques to generate thousands of images of a cell to track the activity.
"Our research would never have been possible without the combination of manual and high throughput microscopy," commented lead researcher Dr Michael Mancini.
Through his innovative use of microscopic techniques, Mancini and his colleagues set up a system that allows multiple quantitative single-cell analyses of how the oestrogen receptor regulates that transcription of genetic messages.
What was intriguing was the cell line contained elements that lit up when the oestrogen receptors were activated. To track the activity the oestrogen receptor was marked with a green fluorescent protein.
When it lit up, it enabled researchers to "see" through a microscope the actions of a protein on the oestrogen receptor.
The technique allowed them to see the receptor move in and out of the nucleus, bind to DNA and remodel the chromatin molecule that makes up the cell's chromosomes.
In addition to this, the system as a whole enabled the researchers to differentiate the manner in which oestrogen receptor responded to a ligand (estradiol) and to a growth factor (epidermal growth factor).
"You can look at DNA occupancy of receptor and coregulators, chromatin modelling and transcription at the same time in the same image, this is a good example of why the approach is being called 'high content analysis'," said Mancini.
"What is really exciting is not only how fast we can collect the data, but the image analysis toolbox is expanding at a remarkably fast rate. This is the beginning of high throughput systems biology."
Personalised medicine is closer to reality now more than ever. As well as predisposition tests, the use of genetic information to prescribe drugs, or combinations of drugs, would be used to treat a patient's disease more effectively.
Several marketed drugs already come with companion diagnostic test to check a patient is suitable to receive the drug, for example Roche/Genentech's Herceptin (trastuzumab), used to treat breast cancer.
The report features in the current issue of the Public Library of Science-One.


