"Cancer Prognosis Gene Found to Control the Fate of Breast Cells

By Wallace Ravven, UCSF News Services | November 30, 2006

Scientists have discovered an unsuspected role for a gene known to be one of the best predictors of human breast cancer outcome.

The gene, called GATA-3, is in a family of genes that guides development of stem cells into mature cells. University of California, San Francisco researchers have now found that GATA-3 is also required for mature mammary cells to remain mature in the adult. In research focusing on mice mammary glands, they found that without GATA-3, mature cells revert to a less specialized, "undifferentiated" state characteristic of aggressive cancer. The new finding suggests that this gene may play a key role in the development of breast cancer, the scientists report in the December 1 issue of the journal CELL.

Cancer researchers know that breast cancers with high GATA-3 expression have a good prognosis. The cancers tend to be well-differentiated -- retaining estrogen receptors and other characteristics of normal mature breast cells. Cancers with low GATA-3 expression tend to be poorly differentiated, with a poor prognosis. The new research may explain why this is so.

"Perhaps the loss of GATA-3 and subsequent failure to maintain this mature state is what leads to loss of differentiation during cancer progression," said Hosein Kouros-Mehr, PhD, a medical student at UCSF and lead author of the new study. "This gene is part of the instruction manual that controls how a stem cell can mature into a normal mammary cell and remain that way for its lifetime. The finding suggests that the differentiation, or maturity, of cells is a process that must be actively maintained throughout the lifetime of an organism."


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