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Scientists Identify More Breast Cancer Genes

Switching off one gene stopped estrogen-linked tumors in the lab

FRIDAY, Aug. 12, 2005 (HealthDay News) -- Canadian researchers say they've identified 153 more genes that promote breast cancer growth, and have found that blocking one gene in particular can stop estrogen-driven breast cancer -- at least in the laboratory.

"Identification of these genes is a slow process," said co-researcher Vincent Giguere. "So far, one per year has been discovered, about 20 in all are known. What we did was use data from the Human Genome Project to engineer a microchip that has about 19,000 pieces of genes on them."

The team then narrowed down where the estrogen receptor was in the genome of breast cancer cells, and identified a large number of genes that respond to the hormone.

The discovery of one gene in particular, named FOXA1, is of importance, Giguere said, because it appears to facilitate estrogen's effects on cancer cells. FOXA1 was required for the estrogen receptor to activate the growth of breast cancer cells.

About two-thirds of breast tumors are estrogen-receptor positive, according to the American Cancer Society, meaning they need estrogen to grow.

"What we did then was remove FOXA1 protein from the cell," said Giguere, the director of the molecular oncology group at McGill University Health Centre in Montreal. "When we do that, the cancer cells cannot grow in response to the estrogen anymore. So, we have identified a gene that is responsible for the growth of breast cancer cells. It dictates how the estrogen hormones can make the cells grow."

"If we can inactivate FOXA1, we can stop the cancer cells from growing," Giguere predicted.

The findings appear in this week's issue of the Proceedings of the National Academy of Sciences.

The next step, Giguere said, is to target FOXA1 in animal models, to see if inactivating it will halt their cancers. Another research team, from the Dana Farber Cancer Institute in Boston, "just identified FOXA1 as being needed to promote breast cancer cell growth, too," Giguere noted.

The discovery represents a major step forward in understanding how estrogen works to promote cancer cell growth, he said.

Eventually, the hope is to develop a drug that would turn off FOXA1, Giguere said, "allowing us to be as precise as possible so as not to affect other actions of estrogen that are beneficial."

Information about the 153 genes may eventually help fight breast cancers, said Dr. Herman Kattlove, a medical oncologist and spokesman for the American Cancer Society.

"The more we know about the genetic makeup of breast cancer cells, the better we will be able to treat it," Kattlove said.

But he also cautioned that the work is preliminary. What is needed, according to Kattlove, is research that shows that blocking the gene works -- and that this genetic interference works better than treatments that are currently available.

More than 211,000 women in the United States will learn they have invasive breast cancer in 2005, according to American Cancer Society estimates, and about 40,000 are expected to die from the disease this year. More than 2 million women in the United States are currently living with breast cancer.

More information

To learn more about breast cancer, visit the American Cancer Society.

SOURCES: Vincent Giguere, Ph.D., director, molecular oncology group, McGill University Health Centre, Montreal; Herman Kattlove, M.D., medical editor, American Cancer Society, Los Angeles; Aug. 9-12, 2005, Proceedings of the National Academy of Sciences

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