Key immune system protein also triggers aggressive breast cancer

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London, Mar 13 : Researchers have discovered that a protein called SATB1 that plays a key role in the immune system is also an essential contributing factor in the most aggressive forms of breast cancer.

The protein plays a critical role in the immune system as it regulating gene expression during the differentiation and activation of T cells that belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity.

Lead researcher Terumi Kohwi-Shigematsu, a scientist in the Life Sciences Division of the Department of Energy's Lawrence Berkeley National Laboratory had discovered SATB1 and has since been investigating its role.

"In breast tumours, SATB1 reprograms the genome to change the expression of hundreds of genes, promoting tumour growth and metastasis," Nature quoted Kohwi-Shigematsu, as saying.

"SATB1's role in breast cancer is a new paradigm for the way tumours progress," she added.

The study conducted using a mouse model revealed that eliminating SATB1, inhibited tumour growth and spread while SATB1 expression in non-aggressive cells led to a more aggressive type of cancer.

For the study, the mice were injected with human aggressive breast cancer cells and after nine weeks the team found that these cells developed into metastatic nodules (tumours) on the lungs.

"Hye-Jung Han of our group started by looking at two dozen breast-cell lines, including normal human epithelial cells" -- epithelial cells are the kind that form the linings of hollow glands in the breast -- "and both nonmetastatic and metastatic breast cancer cells," she said.

"Only the metastatic cells expressed SATB1, with the most aggressive breast cancer cells showing the highest levels of the protein," she added.

The researchers also studied more than 2,000 human primary breast cancer tissue samples. They found that patients with highest levels of SATB1 had low survival rates.

"SATB1 is a key player in the metastasis of breast cancer cells, controlling expression of over a thousand genes," said Kohwi-Shigematsu.

"It increases the expression of genes that promote tumour growth and reduces the expression of tumour suppressors. Among the regulated genes are numerous growth-factor genes and genes affecting cell adhesion, cell signaling, cell-cycle regulation, and other functions," she added.

The study appears in the March 13, 2008 issue of Nature.

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