Breast cancer

13 March 2008

Master breast cancer gene found

Geneticists have identified a super gene which causes breast cancer to metastasise, the deadly process by which the disease spreads to other organs, according to a new study.

Geneticists have identified a super gene which causes breast cancer to metastasise, the deadly process by which the disease spreads to other organs, according to a new study.

Described by the US researchers as a "master regulator," the SATB1 gene alters the behaviour of at least 1 000 other genes within tumour cells, said the study, published in the British journal Nature.

When over-activated it makes cancer cells proliferate, and when neutralised the gene stops the cells from dividing and migrating, the study reported. "SATB1 will be a remarkable target for cancer therapy," said lead scientist Termumi Kohwi-Shigematsu of the Lawrence Berkeley National Laboratory in Berkeley, California.

What the findings mean
The findings could not only pave the way to diagnostic tools that show the likelihood of the disease spreading, she said, but to drugs that could prevent or treat metastasis in breast cancer as well.

Up to now, it was impossible to predict whether cancer cells in a tumour were destined to invade neighbouring tissue, travel through the blood system and form secondary tumours elsewhere in the body. But the SATB1 protein is just such a marker.

A tumour in which it is activated "is destined to metastasise," said Kohwi-Shigematsu. Metastasis is the overwhelming cause of death in patients with solid tumours. Less than 10 percent of women with metastatic breast cancer survive beyond a decade, and just over a quarter make it past five years.

SATB1's normal role in organising other genes - especially related to T-cells that play a critical role in the immune system – was already well known, thanks in part to pioneering research by Kohwi-Shigematsu in the 1990s. The gene had also been identified in breast tumours.

How the study was done
But the new study is the first to establish that "SATB1 is both necessary and sufficient for breast cancer cells to become metastatic," she said.

In experiments on mice, Kohwi-Shigematsu and colleagues "knocked down", or deactivated, the SATB1 gene by removing certain RNAs in the tumour cells upon which the gene depends for multiplying. Messenger RNAs are tiny strings of nucleotides - the basic building blocks of DNA - that ferry the blueprints for constructing proteins from DNA genes to the cell's ribosomes, the factories where proteins are made.

The results, compared to control mice also infected with human metastatic breast cancer cells, were dramatic. Between 125 and 160 metastatic nodules formed in each lung of all the control mice. But in the rodents in which SATB1 was suppressed, the number was between zero and five.

Deliberately over-expressing the gene had the opposite effect, causing the cancer cells to rapidly reproduce and run amok.

Trials on humans planned soon
Translating the study's findings into an effective treatment for cancer would require targeting only the tumours in which the SATB1 gene has become overly active. A drug that blocked the gene throughout the body would compromise its critical - and normal - role in activating the immune system.

Kohwi-Shigematsu is working on a means for delivering an inhibitor via microscopic nanocapsules, and said trials on humans could start within a couple of years. Prognostic tools could be available within a year.

Kohwi-Shigematsu's research is part of a new wave of cancer studies focusing on the genetic origins of the disease. Scientists have come to realise, she said, that there are gene expression patterns called prognosis signatures, genetic profiles found across primary tumours that have metastatic potential. "And now we have identified the protein master regulator for metastatis," she said.

But the most basic question remains to be answered, she added. "What turns SATB1 on during the course of breast cancer progression? We just don't know."

According to the American Cancer Society, about 1.3 million women worldwide are diagnosed each year with breast cancer, and nearly half-a-million succumb to the disease. – (Sapa)

March 2008

Read more:
Major clues to breast cancer
Vaccine to stop breast/ovarian cancer?


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Breast cancer expert

Dr Gudgeon qualified in Birmingham, England, in 1968. She has more than 40 years experience in oncology, and in 1994 she founded her practice, Cape Breast Care, where she treats benign and malignant breast cancers. Dr Boeddinghaus obtained her qualification at UCT Medical School in 1994 and her MRCP in London in 1998. She has worked extensively in the field of oncology and has a special interest in the hormonal management of breast cancer. She now works with Dr Gudgeon at Cape Breast Care. Read more.

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