Scientists have identified a gene they say can promote aggressive breast cancer by acting as a kind of "crime boss," capable of changing the behavior of more than 1,000 genes within tumor cells.
So far, the research has been limited to mice. But if the finding holds true in planned human studies, it may help doctors predict which breast cancers are likely to be aggressive and spread, said Terumi Kohwi-Shigematsu, a senior scientist at the Lawrence Berkeley National Laboratory at the University of California, Berkeley. She is the corresponding author of the study along with her husband, fellow researcher Yoshinori Kohwi, who's also with the Berkeley laboratory.
The gene, SATB1, "is a regulator of whether the cancer spreads," Kohwi-Shigematsu said. "SATB1 was cloned by us in 1992. The gene is already known to be expressed in activated T-cells in animals as part of the immune system response."
SATB1's normal roll in the cell is to "organize" other genes. But when SATB1 is overactivated, the legions of growth-promoting genes that it regulates can run amok, Terumi Kohwi-Shigematsu explained.
Now, the researchers have pinpointed it as the gene that can promote aggressive breast cancer. "SATB1 is a genome organizer, which allows a global change in gene expressions," Kohwi-Shigematsu said. "When it is expressed in breast cancer cells, the cells acquire metastatic activity and growth advantage."
"Once it is expressed," she added, "cancer will spread." Conversely, if SATB1 is silent, cancer doesn't grow.
For the research, the study authors took an established line of breast cancer cells and injected them into laboratory mice. When the scientists disrupted the SATB1 and stopped the expression of the SATB1 protein from the gene, the cancer cells stopped growing and dividing. And when they deliberately expressed the gene in the cancer cells, the tumors grew more aggressively, Kohwi-Shigematsu said.
The findings are published in the March 13 issue of Nature.
Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, who is familiar with the new study, called it "elegant research."
"Basically what they have done is identify a protein that sets up a system that signals various genes within the cells to become abnormal," he said. "It is setting up an environment that allows multiple genes to become 'bad' genes at the same time."
While Kohwi-Shigematsu likened the SATB1 gene's activity to that of a crime "kingpin," Lichtenfeld said he think of it in terms of an orchestra conductor. Either way, genes get altered.
Lichtenfeld cautioned, however, that the finding is new and "a long way from clinical usage."
Kohwi-Shigematsu said her team next plans to study the gene's expression and its effects in people. "We don't know for sure that the cells that show SATB1 expression with the tumors are the ones that metastasize in a patient. But we think most likely that is the case."
If the research continues to bear fruit, the hope is that the presence of the gene's expressed protein will help doctors identify which breast cancers will spread, even in the disease's early stages.
Lichtenfeld added that the finding may also lead to new treatment options for breast cancer.
In another study, published in the March 12 issue of the Journal of the National Cancer Institute, researchers reported another genetic finding. People who carry a rare variant of the AKAP9 gene have a 10 percent increased relative risk of breast cancer in their lifetime if they have one copy of the variant. If they have two copies, the increased relative risk is 17 percent.
More information
To learn more about breast cancer genes, and testing for them, visit the American Cancer Society.
Author: By Kathleen Doheny
HealthDay Reporter
SOURCES: Terumi Kohwi-Shigematsu, Ph.D., senior scientist, Lawrence Berkeley National Laboratory, University of California, Berkeley, Calif.; Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; March 13, 2008, Nature; March 12, 2008, Journal of the National Cancer Institute
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