Breast cancer spread protein

13 Mar 2008
‘Kingpin' gene controls aggressive breast tumours

Geneticists have identified a gene that promotes aggressive breast cancer by altering the behaviour of more than 1,000 other genes within tumour cells. They also found that knocking out this ‘boss' gene causes the cancer cells to stop their runaway proliferation.

The gene, SATB1, is already known to be expressed in breast tumours and is a key factor in the process of metastasis, the spread of cancerous cells to other locations in the body.

This week's Nature reports that Terumi Kohwi-Shigematsu and co-workers from the University of California, USA, studied SATB1 expression levels with human breast cancer and non-malignant cell lines and with human tissue
specimens from primary tumours and adjacent tissues.

Prognostic values of SATB1 were evaluated by anti-SATB1 immunostaining of breast tissue microarrays containing 2,000 cases with clinical follow-up records.

Tumour growth and intravasation, part of the process of metastasis, were studied by injecting neo-expressing human cancer cells near the mammary glands in mice. Tumour growth was monitored for 6-7 weeks and the presence of human cells in blood and lung were determined.

Tumour cells were intravenously injected in to mice and cancer spread to lung was determined by quantifying lung colonisation after 9-10 weeks. Colonised lung and mammary tumours were confirmed by pathological analyses.

In the mouse models, they found that disrupting SATB1 stops cancer cells from dividing and spreading. Conversely, deliberately expressing this gene in cancer cells causes them to form very aggressive tumours.

This is consistent with SATB1's normal role in the cell, as an ‘organiser' of other genes, the researchers add. Aggressive tumours therefore form when this gene is over activated, and the ‘mob' of growth-promoting genes that it controls begins to run amok.