Scientists in Scotland have identified a gene that plays a key role in the spread of HER2 positive breast cancer to other parts of the body, raising hopes of a new treatment for this common form of breast cancer.

Research leader Dr Elad Katz, from the Breakthrough Breast Cancer Research Unit at the University of Edinburgh, and colleagues describe their research and discovery of the new gene, called C35, in a paper that was published online in the British Journal of Cancer on 13 July.

HER2 positive breast cancer is a type of breast cancer where an overexpression of the HER2/neu gene and its associated protein HER2 (Human Epidermal growth factor Receptor 2) is linked to increased disease recurrence and worse prognosis.

It accounts for 1 in 5 of all breast cancer cases and affects about 9,000 women a year in the UK, including around 800 in Scotland. Herceptin (trastuzumab) targets the HER2 positive cancer but it is not effective in all patients, hence the need for new drug targets to help save the lives of thousands of women with this form of the disease and who do not respond to Herceptin.

Katz and colleagues decided to take a look at C35 because while it is over-expressed in many invasive breast cancers, its function is unknown.

For the study they took specimens from 122 breast cancers and using a method involving tissue microarrays, they examined the association between C35 and HER2 expression.

They found that in primary breast cancers, high levels of C35 mRNA gene expression were linked with HER2 gene amplification, and using lab cultures, were able to show that high levels of C35 protein expression were linked with hallmarks of how cancer cells are formed: for instance they grew colonies in soft agar and then showed they invaded collagen matrices (the scaffolding that gives tissue its structure) to form larger three-dimensional structures.

The transformed cells also showed other characteristics of cells undergoing transition to tumor cells (eg “epithelial to mesenchymal transition”, changes to cell shape, and “down-regulation of epithelial markers, such as E-cadherin and keratin-8”).

And the researchers also found that part of the transformation triggered by C35 depended on Syk kinase, an enzyme that mediates important signals from C35.

Katz and colleagues concluded that:

“C35 functions as an oncogene in breast cancer cell lines. Drug targeting of C35 or Syk kinase might be helpful in treating a subset of patients with HER2-amplified breast cancers.”

Professor David Harrison, Director of the Breakthrough Breast Cancer Research Unit at the University of Edinburgh, told the press that:

“This is an important development because we now know one of the key triggers to the spread this type of cancer.”

Researchers at Breakthrough Breast Cancer are excited by this discovery because there are already drugs in development that could target C35, offering a new treatment for HER2 positive breast cancer.

“It is exciting to know there is a drug out there which could potentially stop this process happening and save the lives of women with breast cancer,” said Harrison.

“We now need to do more work in the lab to prove this concept before we can start patient trials,” he added.

Katz agreed:

“We are at an early stage, but there is now a real possibility there could be a new treatment for women with HER2 positive breast cancer,” he said.

“A gene on the HER2 amplicon, C35, is an oncogene in breast cancer whose actions are prevented by inhibition of Syk.”
E Katz, S Dubois-Marshall, A H Sims, D Faratian, J Li, E S Smith, J A Quinn, M Edward, R R Meehan, E E Evans, S P Langdon and D J Harrison.
British Journal of Cancer, Published online 13 July 2010

Additional sources: Breakthrough Breast Cancer, wikipedia.

Written by: Catharine Paddock, PhD