CHAMPAIGN, Ill. Researchers have identified a protein long known to regulate gene expression as a potent suppressor of breast cancer growth. Their study, in the journal Oncogene, is the first to demonstrate how this protein, known as Runx3, accomplishes this feat.
"People suggested that Runx3 might be a tumor suppressor in breast cancer because they found that it is down-regulated in a lot of breast cancer cell lines and breast cancer tissues," said University of Illinois medical biochemistry professor Lin-Feng Chen, who led the study. But no previous studies uncovered direct evidence to support that idea, he said.
In the new study, Chen and his colleagues at Nagasaki University discovered that a significant proportion of mice lacking one of two Runx3 genes spontaneously developed mammary gland tumors at 14 or 15 months of life an age corresponding to age 40 to 50 in humans.
"We found mammary tumors growing in about 20 percent of the female mice lacking a copy of the Runx3 gene," Chen said. None of the mice with two normal copies of the gene developed tumors.
The researchers also found that estrogen receptor alpha (ER-alpha), a well-known culprit in the development of many breast tumors, was up-regulated in the mouse tumors. ER-alpha is overexpressed in about 75 percent of human cases of breast cancer, and enhanced ER-alpha expression in normal breast tissue is associated with an increased risk of breast cancer, Chen said.
Circulating estrogen binds to ER-alpha and initiates a chain of events that alter gene expression in the targeted cell. This is a normal part of cellular signaling, but in ER-positive breast cancers, the overexpression of ER-alpha leads to enhanced tumor cell survival, growth and proliferation.
The researchers found that when Runx3 was re-introduced into ER-alpha positive breast cancer cell lines, it suppressed the g
|Contact: Diana Yates|
University of Illinois at Urbana-Champaign