Volume 10 Supplement 2

Breast Cancer Research 2008

Open Access

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

  • E Katz1,
  • D Faratian1,
  • JMS Bartlett1,
  • K MacLeod1,
  • H Pedersen1,
  • A Larionov1,
  • EM Smith2,
  • AP Howell2,
  • JM Dixon1,
  • EE Evans2,
  • SP Langdon1 and
  • DJ Harrison1
Breast Cancer Research200810(Suppl 2):P77

https://doi.org/10.1186/bcr1961

Published: 13 May 2008

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.

Authors’ Affiliations

(1)
Cancer Research Centre, University of Edinburgh
(2)
Vaccinex Inc.

Copyright

© BioMed Central Ltd 2008

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