1. ¹Institute of Pathology, Helmholtz Centre Munich, German Research Centre for Environmental Health, Neuherberg D-85764, Germany
2. ²Institute of Molecular Radiation Biology, Helmholtz Centre Munich, German Research Centre for Environmental Health, Neuherberg D-85764, Germany
3. ³Institute of Radiation Biology, Helmholtz Centre Munich, German Research Centre for Environmental Health, Neuherberg D-85764, Germany
4. ⁴Klinik für Strahlentherapie, Technische Universität München, Ismaninger Strasse 22, München 81675, Germany
5. ⁵Institut für Pathologie, Technische Universität München, Trogerstr. 18, München 81675, Germany
6. ⁶Department of Oncology and Pathology, Karolinska Institute and Hospital, Stockholm S-17176, Sweden
7. ⁷University Department of Surgery, Glasgow Royal Infirmary, Queen Elizabeth Building, 10 Alexandra Parade, Glasgow G31 2ER, UK
8. ⁸Endocrine Cancer Group, Cancer Research Centre, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK

Correspondence: Dr M Aubele, Helmholtz Zentrum München, Institut für Pathologie, Ingolstädter Landstrasse 1, Neuherberg 85764, Germany. E-mail: aubele@helmholtz-muenchen.de

Received 3 June 2008; Revised 18 August 2008; Accepted 18 August 2008; Published online 9 September 2008.

Abstract

The cytoplasmic tyrosine kinase PTK6 (BRK) shows elevated expression in approximately two-thirds of primary breast tumours, and is implicated in EGF receptor-dependent signalling and epithelial tumorigenesis. Using immunohistochemistry, we performed a retrospective study on 426 archival breast cancer samples from patients with long-term follow-up and compared the protein expression levels of PTK6, the HER receptors, Sam68 (a substrate of PTK6), and signalling proteins including MAP kinase (MAPK), phosphorylated MAPK (P-MAPK), and PTEN. We show that PTK6 expression is of significant prognostic value in the outcome of breast carcinomas. In multivariate analysis, the disease-free survival of patients of 240 months was directly associated with the protein expression level of PTK6 (P0.001), but was also inversely associated with nodal status (P0.001) and tumour size (P0.01). PTK6 expression in tumour tissue significantly correlated (P0.05) with the expression of PTEN, MAPK, P-MAPK, and Sam68. To investigate whether these correlations may be due to molecular interactions between PTK6 and these proteins, we used protein extracts from the T47D cell line for immunoprecipitation and western blot analysis. By this, interactions could be demonstrated between PTK6 and MAPK, P-MAPK, HER2/neu, HER3, HER4, PTEN, and Sam68. On the basis of these results, we suggest that PTK6 may serve as a future target for the development of novel treatments in breast cancer.