Breast-cancer gene probe

A researcher from UCD may have discovered a way to predict how well a patient does after receiving a diagnosis of breast cancer…

A researcher from UCD may have discovered a way to predict how well a patient does after receiving a diagnosis of breast cancer, writes Dick Ahlstrom

A young postgraduate researcher has identified a marker that may be able to predict how well a woman does after the diagnosis of breast cancer. Her work is also telling us a great deal about the biochemical changes seen in cells during puberty.

Jean McBryan is a research student in UCD's school of biochemcial and biomedical science and the university's Conway Institute. Working under supervisor Prof Finian Martin, she has been studying CITED1, a gene involved in breast development during puberty.

Her CITED1 work last week helped her win the top prize in a new research competition, which took place last week during the sixth annual UCD Conway Festival of Science. The Festival is an exposition of the important research being conducted at the Conway and the new gold medal award programme allows some of Ireland's most promising young researchers to shine.

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McBryan studied CITED1 as a fourth-year undergraduate and decided to continue the work during her PhD. With colleagues she used microarrays capable of detecting the thousands of proteins being expressed in the mammary glands of mice, watching how they changed during puberty.

"The intent has always been to follow development during puberty," says McBryan. There are a lot of changes taking place very rapidly, with genes up and down regulated. "So there must be a lot of control there. We wanted to try to learn about those controls," she adds.

"We wanted to know if CITED1 was involved and so we looked at mice without the CITED1 gene."

Before puberty the mammary gland is little more than a bud but tissues begin to form in response to gene expression, forming a tree-like shape, she explains.

"In mice that didn't have the CITED1, the tree didn't form at all. This confirmed CITED1 plays a part in mammary gland development."

She began examining the biochemistry behind this more closely. She was looking for signs of interaction between CITED1 and estrogen receptors given estrogen's known role in development during puberty but also because CITED1 and estrogen receptors are expressed in the same cells.

She discovered that in fact CITED1 may have a powerful influence on the performance of the estrogen receptors. Although levels of estradiol, an important hormone in initiating puberty development, were not altered in the mice without the CITED1 gene, the activity of other genes controlled by estrogen were lowered.

"What we are hoping to do next is learn more about that pathway," says McBryan. This will involve confirming her belief that the control of estrogen levels is in some way associated with CITED1.

She is also looking at CITED1 involvement in breast cancer. The gene is known to be expressed in human breast tumour samples and a study of 300 samples identified a strong positive link between CITED1 and estrogen receptor activity.

The levels of CITED1 present seemed to have some influence on the overall survival rates in the sample of 300 patients. "The patients with higher levels of CITED1 tended to survive better than than those with low levels of CITED1," McBryan explained.

Measuring CITED1 levels could provide a way to predict patient outcomes. "More work is needed to find out what is going on and how it could be used," adds McBryan.

Her research is funded by an award from the Irish Research Council for Science, Engineering and Technology and by Science Foundation Ireland.

The Fannin Healthcare Group sponsored the medal award and cash prizes for the three winners of the competition, including a €500 award for McBryan.

The second place award went to Eoin Cummins who is studying the biochemistry of cells that are starved of oxygen and third place went to Sarah McClelland who is looking at how linoleic acid may work against hardening of the arteries.