title: Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients.
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 >or=240 months was directly associated with the protein expression level of PTK6 (P<or=0.001), but was also inversely associated with nodal status (P<or=0.001) and tumour size (P<or=0.01). PTK6 expression in tumour tissue significantly correlated (P<or=0.05) 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.
authors.affiliation: Institute of Pathology, Helmholtz Centre Munich, German Research Centre for Environmental Health, Neuherberg D-85764, Germany. aubele@helmholtz-muenchen.de
authors.forename: M
authors.initials: M
authors.lastname: Aubele
authors.forename: A K
authors.initials: AK
authors.lastname: Walch
authors.forename: N
authors.initials: N
authors.lastname: Ludyga
authors.forename: H
authors.initials: H
authors.lastname: Braselmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: B
authors.initials: B
authors.lastname: Luber
authors.forename: G
authors.initials: G
authors.lastname: Auer
authors.forename: S
authors.initials: S
authors.lastname: Tapio
authors.forename: T
authors.initials: T
authors.lastname: Cooke
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human
references.citation: Oncogene. 2003 Aug 7;22(32):5006-10
references.pmid: 12902983
references.citation: Br J Cancer. 2004 Oct 18;91(8):1532-42
references.pmid: 15480434
references.citation: J Biol Chem. 2005 Nov 18;280(46):38639-47
references.pmid: 16179349
references.citation: Br J Cancer. 2007 Mar 12;96(5):801-7
references.pmid: 17299391
references.citation: J Biol Chem. 2005 Jan 21;280(3):1982-91
references.pmid: 15539407
references.citation: Oncogene. 2000 Nov 16;19(48):5471-6
references.pmid: 11114724
references.citation: Cancer Res. 2007 May 1;67(9):4199-209
references.pmid: 17483331
references.citation: Oncogene. 1997 Aug 14;15(7):799-805
references.pmid: 9266966
references.citation: Oral Oncol. 2004 Nov;40(10):1040-7
references.pmid: 15509496
references.citation: Anticancer Drugs. 2004 Feb;15(2):107-11
references.pmid: 15075665
references.citation: J Pathol. 2003 Jul;200(3):290-7
references.pmid: 12845624
references.citation: Cancer. 2003 Jul 1;98(1):18-23
references.pmid: 12833450
references.citation: Mod Pathol. 2001 Jul;14(7):672-6
references.pmid: 11454999
references.citation: Clin Cancer Res. 2002 Feb;8(2):361-7
references.pmid: 11839650
references.citation: J Biol Chem. 2004 Dec 24;279(52):54398-404
references.pmid: 15471878
references.citation: Oncogene. 1994 Aug;9(8):2383-90
references.pmid: 8036022
references.citation: Blood. 2003 Apr 15;101(8):3181-7
references.pmid: 12515730
references.citation: Clin Cancer Res. 1999 Jul;5(7):1767-77
references.pmid: 10430081
references.citation: Nature. 1994 Apr 28;368(6474):867-71
references.pmid: 7512694
references.citation: Oncogene. 2006 Aug 10;25(35):4904-12
references.pmid: 16568091
references.citation: Oncogene. 2003 Jul 3;22(27):4212-20
references.pmid: 12833144
references.citation: Cancer Invest. 1990;8(2):253
references.pmid: 1976032
references.citation: Histopathology. 2006 Sep;49(3):248-55
references.pmid: 16918971
references.citation: Cell Cycle. 2005 Sep;4(9):1239-46
references.pmid: 16082217
references.citation: Mol Cell Biol. 2004 Dec;24(24):10558-72
references.pmid: 15572663
references.citation: Breast Cancer Res. 2007;9(6):R79
references.pmid: 17997837
references.citation: Arch Pathol Lab Med. 2007 May;131(5):767-72
references.pmid: 17488163
references.citation: Mol Cell Biol. 2000 Aug;20(16):6114-26
references.pmid: 10913193
references.citation: Clin Cancer Res. 2005 Jul 1;11(13):4835-42
references.pmid: 16000581
references.citation: Br J Cancer. 2007 Aug 20;97(4):453-7
references.pmid: 17667926
references.citation: Histopathology. 1991 Nov;19(5):403-10
references.pmid: 1757079
references.citation: Oncogene. 2004 May 6;23(21):3781-9
references.pmid: 15021911
references.citation: J Cell Physiol. 2006 Mar;206(3):702-8
references.pmid: 16245316
references.citation: Breast Cancer Res Treat. 2003 Aug;80(3):353-61
references.pmid: 14503808
references.citation: J Pathol. 2005 Apr;205(5):592-6
references.pmid: 15685689
references.citation: J Clin Oncol. 2005 Apr 10;23(11):2469-76
references.pmid: 15753463
references.citation: J Biol Chem. 1996 Nov 29;271(48):30956-63
references.pmid: 8940083
references.citation: Mol Cell Biol. 2006 Jul;26(13):4949-57
references.pmid: 16782882