Abstract
Abstract Abstract #3073 Background: Elevated expression of the cytoplasmic tyrosine kinase PTK6 (breast tumor kinase, BRK) occurs in approximately two-thirds of primary breast tumors, where it is implicated in EGF receptor-dependent signaling and epithelial tumorigenesis. The role of PTK6 in breast cancer development and prognosis is unclear, its function in-vivo remains undefined.
 Material and Methods: We performed a retrospective study of PTK6 expression in 426 archival breast cancer samples from patients with long term (≥240 months) follow up. Immunohistochemical analysis of the following proteins was determined: PTK6, all 4 HER receptors, Sam68 (a substrate of PTK6), and the signalling proteins MAP kinase (MAPK), phosphorylated MAPK (P-MAPK), and PTEN. Correlations between markers were determined, and the prognostic value of parameters by univariate and multivariate survival analysis. We compared PTK6 gene copy number with the protein expression levels using FISH analysis.
 Results: The disease-free survival of patients ( ≥240 months) was positively correlated with PTK6 protein expression, and was inversely correlated with nodal status and tumor size (p≤0.01). A time dependence for the prognostic value of key markers was evident, with HER2/neu only showing prognostic significance at early time points (60 months).
 PTK6 expression in tumor tissue significantly correlated with the expression of PTEN, MAPK, P-MAPK, and Sam68 (p≤0.05). To investigate whether these correlations may be due to molecular interactions, we used the T47D cell line for immunoprecipitation and Western Blot analysis. Co-precipitation-type protein-protein interactions could be demonstrated between PTK6 and MAPK, P-MAPK, HER2/neu, HER3, HER4, PTEN, and Sam68.
 Quantitative analysis revealed an increased PTK6 gene copy number in 75% of the tumors. Polysomy of chromosome 20 was responsible for most cases (47%) whilst gene amplifications were less frequent (28%).
 Discussion: We show that PTK6 protein expression is of significant prognostic value in predicting the long term outcome of breast carcinomas. Further, several potential binding partners were identified, indicating the involvement of PTK6 in three main signal transduction pathways.
 Supported by: Deutsche Krebshilfe # 10379 / EU LSHC-CT-2004-503426. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3073.
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