'Kingpin' gene controls breast tumour growth and spread
WEDNESDAY 12 MARCH 2008
Scientists have identified a gene that promotes aggressive breast cancer by altering the activities more than 1,000 other genes.
A report in the latest issue of Nature reveals that the gene, SATB1, is a key player in metastasis, the process by which cancer cells move away from the primary tumour site and settle in other parts of the body.
The new results suggest the gene plays an 'organiser' role in healthy cells, controlling a large number of other genes and recruiting enzymes that regulate the structure of chromatin, the DNA and protein complex that makes up chromosomes inside the cell's nucleus.
SATB1 has previously been found in high levels in breast tumours and researchers at the University of California have now discovered that, by deliberately switching the gene on in breast cells, they were able to form highly aggressive tumours in the laboratory.
In addition, they found that blocking the activity of this 'kingpin' gene prevented cancer cells from dividing and spreading in mice.
"We have shown that a variety of genes involved in many aspects of tumorigenesis (cancer development) are regulated by SATB1, indicating that a large group of SATB1-targeted genes collectively induce tumour growth and metastasis," the researchers wrote.
The researchers noted that SATB1 expression is not only involved in the latter stages of cancer, but was also observed in primary breast tumours before the disease had spread to the lymph nodes.
They also revealed that the level of SATB1 activity in cancer cells could potentially be used to predict the likelihood of disease progression in patients with early-stage breast cancer.
They concluded: "Our findings suggest a new paradigm in tumour progression, in which SATB1 functions as a genome organiser during tumorigenesis to re-programme expression and promote metastasis.
"Future studies will address how applicable this concept is to other tissues. SATB1 may be useful as a therapeutic target for metastatic breast disease."
Dr Kat Arney, senior science information officer at Cancer Research UK, said: "This fascinating piece of research suggests that the way DNA is arranged within cells may contribute to cancer.
"We've known for some time that SATB1 can reorganise DNA and alter patterns of gene activity, and now it seems that if this molecule behaves inappropriately, it could cause changes that lead to cancer.
"Even more interesting is the fact that removing SATB1 apparently reverses these changes, which suggests that it could provide an exciting lead for treating breast cancer in the future."
Arsenic-based therapy may destroy leukaemia-initiating cells
Exercise reduces the risk of breast cancer in most women
Scientists identify genetic changes involved in childhood cancer
Mathematical model predicts breast tumours grow faster in younger women
Smoking death risks significantly reduced within five years of quitting
Researchers suggest playgroups could be linked to lower leukaemia risk
Healthy habits linked to higher quality of life among cancer survivors
Study demonstrates drug's effect on breast cancer stem cells
Mums unaware of breastfeeding benefits
'Encouraging' uptake in HPV vaccination trial
