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Collaborators in the Melbourne-based Cooperative Research Centre for Cellular Growth Factors (CRC-CGF) have made a significant discovery concerning a mechanism that controls the spread of cancer cells.

Researchers from the CSIRO, the Ludwig Institute for Cancer Research and the Walter and Eliza Hall Institute of Medical Research have determined the three-dimensional structure of the ErbB2 receptor, a protein known to be involved in several types of cancer, including about 30% of all breast cancers.

This discovery follows the announcement last year that the same group of scientists had determined the structure of another member of this family of cancer cell receptors, the EGF (epidermal growth factor) receptor bound to its growth factor TGFa.

Cancer involves the uncontrolled growth of cells as a result of the dysfunction of a number of cellular proteins. Both the EGF receptor and ErbB2 are such proteins and are seen as major targets for the development of new cancer therapies.

While the EGF receptor has to be activated by a corresponding hormone in order for cancerous cells to develop, the real puzzle was how ErbB2 managed to activate cell growth without being able to bind any known hormone.

“The 3D structure reveals that ErbB2 is already in the activated state, poised to interact with other partners when they become available” said Dr Tom Garrett of the Walter and Eliza Hall Institute, the structural biologist on this project.
“ErbB2 is like a gun that is pre-cocked. Binding to other members of the same family of proteins pulls the trigger which sets off cell division.”

Dr Tim Adams from the CSIRO said this work provided the fundamental information required for a drug development program that was now underway in the CRC for Cellular Growth Factors.

“The ultimate objective is to design precisely targeted drugs that sabotage the operation of this receptor family and thus weaken cancer cells which are dependent on this system. Now that we know how ErbB2 works we are aiming to block this action and stop the signal for cell growth.”

Professor Tony Burgess, Director of the Ludwig Institute for Cancer Research said “These discoveries, along with related discoveries by scientists in the United States and Japan, have now given us a much clearer picture of how this important family of proteins work”. Professor Burgess and his colleagues have invited most of the key researchers in the field to come to Victoria to discuss the implications of these exciting discoveries during a three-day workshop in late March. “Their enthusiastic participation reflects their view of the importance of the contributions made by Australian scientists in this area of cancer research”, he said. “The research has been a wonderful collaboration between the three Institutions involved and has been greatly facilitated by the CRC program.”

The findings of the CRC-CGF are published in the February 2003 issue of the prestigious journal, “Molecular Cell.”

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Media enquiries should directed to:

Mr Warrick Glynn
CSIRO Health Sciences and Nutrition
Tel: 03 9662 7344, Mobile: 0403 117 846

or

Mr Brad Allan
The Walter and Eliza Hall Institute of Medical Research
Phone: (+61) 3 9345 2345
Mobile: 0403 036 116
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