C35 overexpression defines subsets of human breast cancer and its immunoreceptor tyrosine-based activation motif represents a novel treatment target

bcr1961 BCJ Poster presentation C35 overexpression defines subsets of human breast cancer and its immunoreceptor tyrosine-based activation motif represents a novel treatment target Katz E Faratian D Bartlett JMS MacLeod K Pedersen H Larionov A Smith EM Howell AP Dixon JM Evans EE Langdon SP Harrison DJ

Cancer Research Centre, University of Edinburgh, UK

Vaccinex Inc., Rochester, NY, USA

Breast Cancer Research Breast Cancer Research 2008 Meeting abstracts http://breast-cancer-research.com/supplements/notes/BCR-vol10-suppl2-info.pdf Breast Cancer Research 2008 London, UK

13 May 2008

http://www.breastcancercampaign.org/ 1465-5411 2008 10 Suppl 2 P77 http://breast-cancer-research.com/content/10/S2/P77 10.1186/bcr1961 13 5 2008 2008 BioMed Central Ltd

C35 is a protein overexpressed in invasive breast cancer. The C35 gene is located on chromosome 17, next to ERBB2/HER2. C35 encodes a canonical immunoreceptor tyrosine-based activation motif (ITAM) sequence. ITAM-containing proteins have key signalling roles in the hematopoietic system and in oncogenic retroviruses. The ITAM interacts with Syk kinase, which mediates downstream signalling events.

C35-overexpressing breast tumours were found to be of two subsets. In one subset, C35 is coexpressed with HER2. The second subset is found within the basal-like carcinoma group. In order to evaluate the therapeutic potential of targeting C35 ITAM/Syk signalling, we utilised 3D cell cultures. Transformed cell lines act in a manner resembling their in vivo behaviour when grown in 3D cultures, on reconstituted basement membrane. Using this method, C35-expressing cells formed enlarged structures in both an ITAM-dependent and Syk-dependent manner. Furthermore, BT474 cells coexpressing C35 and HER2 formed more normal 3D structures when treated with a combination of Herceptin and Syk inhibitors.