Breast tumor kinase/protein tyrosine kinase 6 (Brk/PTK6) activity in normal and neoplastic biliary epithelia

摘要: Background & Aims Breast tumor kinase (BRK) augments proliferation and promotes cell survival in breast cancers via interactions with SH2 SH3 ligand-containing proteins, such as receptor tyrosine kinases (RTK; e.g. EGFR, ErbB2/neu). Since RTK contribute to cholangiocarcinoma (CC) evolution we probed BRK protein expression function normal CC livers. Methods Immunohistochemical staining of livers (n=93) a tissue microarray three an immortalized human cholangiocyte lines (real-time PCR, Western blotting, siRNA) were used study the functional relationships between BRK, ErbB2, SAM68, SPRR2a. Results was expressed intrahepatic bile ducts; all majority showed strong expression. Multiplex immunostaining/tissue cytometry immunoprecipitation studies showed: 1) co-localized EGFR ErbB2/neu; 2) high /EGFR -co-expressing cells had significantly higher Ki67 labeling and; 3) stronger seen perihilar distal than directly correlated differentiation. In lines, augmented response exogenous EGF, whereas siRNA reduced growth. The ligand-containing, SPRR2A activated pTyr342 which turn, phosphorylated causing nuclear localization increased similar observations cancers. Conclusion can interact RTK, augmenting growth interfering inhibitors (SAM68). Therapeutically targeting (in addition RTK) should be benefit for treatment.