Mar 13, 2008

'Bossy' protein may be cancer link

By Betsy Mason / Bay Area News Group

Whether breast cancer spreads aggressively or not may come down to a single protein that controls more than 1,000 genes.

If this bossy protein, known as SATB1, is present in a breast tumor, these genes behave badly and the cancer is far more likely to spread to other parts of the body, or metastasize, according to researchers at Lawrence Berkeley Laboratory.

"Hopefully someday in the future we can devise a therapy by targeting SATB1," said Terumi Kohwi-Shigematsu, an author of the study that appears this week in Nature.

While studying the protein's important role in controlling blood cells that are key to the immune system, Kohwi-Shigematsu's team discovered the protein's dark side.

"We noticed that SATB1 can turn into a crime boss in breast cancer cells," she said. "It's a bad guy."

The team took a closer look at the protein's effect on breast cancer by watching how human breast cancer cells behave in mice.

They took aggressive metastatic cancer cells and removed the SATB1 protein from them and then injected them into the bloodstream of mice. The mice formed normal lung tumors with smooth, discrete edges that rarely spread beyond the lungs.

Next, they took regular, non-metastatic human breast cancer cells and added SATB1 before injecting them into the mice. These mice developed aggressive lung tumors that often spread to other parts of the body.

This shows that this single protein can turn on genes that cause breast cancer to run wild, and that if the protein isn't there the cancer cells remain mellow.

When SATB1 calls the shots, genes that are known to be bad breast cancer genes are increased, and genes that can hold tumors in check are decreased.

"We see over a thousand genes that change their expression level," said Kohwi-Shigematsu.

The team also tested human breast cancer cells from 28 different cases. They found that the survival time from diagnosis was correlated with the level of SATB1 in the cells. High amounts of the protein correlated with the shortest survival, while the absence of the protein correlated with longer survival.

A big question that remains is what controls whether SATB1 is present or not.

"There must be a turning point where breast cancer cells start producing SATB1," Kohwi-

Shigematsu said. "If we can find that and stop it, we can confine breast cancer cells to the breast."

There are several hurdles to be cleared before the discovery can become a treatment, including finding a way to turn off the protein such as an antibody or chemical, and devising a way to deliver it to the cells.

The detection of SATB1 in a patient's cancer cells could also be used to evaluate that patient's prognosis and help determine a course of treatment. High levels of the protein, even in a very small tumor caught very early, means the cancer will almost undoubtedly metastasize if not treated swiftly and aggressively.

This technique could be available relatively quickly, Kohwi-Shigematsu said, but it will take interest from a drug company or other industry partner to get it off the ground.

"We really need a collaborator for this."