First Step Towards Switching Off Breast Cancer And Leukaemia

Australian scientists have identified a way to 'switch off' a molecule, a
key player in the molecular processes that trigger breast cancer and certain
forms of leukaemia.


The molecule, known as Gab2, operates downstream of a major breast cancer
oncogene, HER2, the target of the drug Herceptin.


A research team from the Garvan Institute of Medical Research, led by
Professor Roger Daly, has found a novel way of blocking signals to and from
Gab2, preventing it from fulfilling its role in cell proliferation. The
finding is published online in the EMBO Journal.


In 2002, Professor Daly identified the important role of Gab2 in breast
cancer. His task since then has been to work out exactly how Gab2 functions,
and how to stop it.


"Gab2 is a signalling protein, which means that it's involved in
transmitting signals from the cell surface to the interior of the cell,
instructing it to do specific things, such as divide or migrate" he said.


"Gab2 performs a number of signalling roles in normal cells throughout the
body, and is usually switched off when it's not needed. Our task has been to
work out how the body switches off Gab2, so that we can mimic that process
in abnormal cells."


"We've identified a completely novel mechanism for switching off Gab2. This
uses another molecule that attaches to Gab2 and acts as a kind of shield,
preventing it from transmitting further proliferative signals."


"This binding partner, or 'off switch', is called 14-3-3, and is used to
disable Gab2 in a number of cellular settings, when it is no longer needed."


"As Gab2 plays key roles in signalling systems that underpin both normal
physiological responses and oncogenesis, it's very important to understand
its control mechanisms."


"Our next step will be to obtain more structural information about how
14-3-3 shields Gab2. Once we know that, it should be possible to design
drugs to combat Gab2-activated diseases in novel ways."


About Garvan


The Garvan Institute of Medical Research was founded in 1963. Initially a
research department of St Vincent's Hospital in Sydney, it is now one of
Australia's largest medical research institutions with approximately 400
scientists, students and support staff. Garvan's main research programs are:
Cancer, Diabetes & Obesity, Immunology and Inflammation, Bone, and
Neuroscience. Garvan's mission is to make significant contributions to
medical science that will change the directions of science and medicine and
have major impacts on human health. The outcome of Garvan's discoveries is
the development of better methods of diagnosis, treatment, and ultimately,
prevention of disease.

The Garvan Institute of Medical Research


View drug information on Herceptin.