Discovery has implications for breast, ovarian cancer treatments

MINNEAPOLIS/ST.PAUL (Jan. 8, 2008)—A University of Minnesota cancer researcher has discovered how key genes cause breast and ovarian cancer cells to either multiply or die. This discovery opens the door to developing drugs that target these E2F1 target genes, balance their dual functions, and give women diagnosed with breast or ovarian cancer a greater chance for long-term survival.

Timothy Hallstrom, Ph.D., assistant professor and scientist with the Masonic Cancer Center, collaborated with researchers at Duke University to make this discovery. The finding is reported today in the journal Cancer Cell.

"Cancer researchers have known for some time that certain proteins regulate genes that are essential for cancer cells to either proliferate or die off," Hallstrom said. "With our discovery, we now also know which specific genes serve the dual functions of turning cancer cells on or off, and how these functions operate in breast and ovarian cancers."

According to Hallstrom, cancer most frequently begins when pathways in the body known as the Rb and PI3K pathways become overly active through mutations. This new research now shows that the activity of both of these pathways converges on E2F1 to block the expression of these target genes that cause cancer cells to die.

Hallstrom and his colleagues used gene expression data from tissue samples taken from 408 women diagnosed with breast cancer and 153 women with ovarian cancer. They found that increased activity in the PI3K pathway repressed the expression of the death genes, allowing cancer cells to live. On the other hand, low PI3K activity allowed the expression of cell death genes and killed the cancer cells. They also found that cancer cell death equated with a good prognosis for patients.

Poor prognosis was found for patients in whom this function was repressed, and the cancer cells proliferated.

"These findings open the door for testing the therapeutic value of chemically inhibiting PI3K signaling in these tumors, restoring expression of cell death genes, and thereby improving the prognosis of these patients," he said. "Our finding is another step forward in understanding how cancer circumvents innate cell death pathways, and emphasizes the importance of putting in balance the dual functions of E2F1 target genes."

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This study was sponsored with a grant from the National Institutes of Health. Researchers working with Hallstrom on this study were Seiichi Mori and Joseph R. Nevins, both at Duke University.

The Masonic Cancer Center is part of the University's Academic Health Center and is designated a Comprehensive Cancer Center by the National Cancer Institute. To learn more about the Cancer center, visit www.cancer.edu or call the information line at 612-624-2620.

Media contacts:

Masonic Cancer Center: Mary Lawson, Public Relations Director, 612-624-6165, 612-203-0819 (cell), mlawson@umn.edu

University of Minnesota Academic Health Center: Sara Buss, 612-626-7037