title: Tyrosine kinase expression profile in clear cell renal cell carcinoma.
abstract: OBJECTIVE
  To profile different tyrosine kinase (TK) expression patterns in clear cell renal carcinoma (ccRCC).
  
  
  METHODS
  We analysed mRNA expression levels of 89 receptor and non-receptor TK in corresponding cancer and normal renal tissue from 5 patients with ccRCC using the TaqMan Low-Density Array technology. In order to confirm aberrant TK expressions, a subsequent analysis of 25 ccRCC and corresponding normal renal tissues was performed, applying quantitative real-time PCR. To confirm mRNA expression levels on protein level, we studied ERBB4 and HCK using immunohistochemistry.
  
  
  RESULTS
  A total of 12 TK were significantly upregulated in ccRCC (ABL2, FLT1, BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK, PTPRC, FYN and CSK), coherently 7 TK demonstrated a down-regulation (ERBB4, PDGFRA, NRTK3, SYK, ERBB2, FGFR3 and PTK7). These findings were validated by the utilization of RT-PCR for ABL2, FLT1 BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK and vice versa for ERBB4 and PDGFRA. Immunohistochemistry revealed ERBB4 expression to be significantly lower in ccRCC in comparison to papillary RCC, chromophobe RCC, renal oncocytoma and normal renal tissue (P < 0.001). HCK protein expression was reduced in ccRCC in contrast to papillary RCC (P < 0.001) or oncocytoma (P = 0.023), but similar to chromphobe RCC (P = 0.470), sarcomatoid RCC (P = 0.754) and normal renal tissue (P = 0.083). Neither ERBB4 nor HCK were correlated (P > 0.05) with clinical-pathological parameters.
  
  
  CONCLUSIONS
  TK constitute valuable targets for pharmaceutical anti-cancer therapy. ERBB4 and HCK depict significantly lower expression levels in renal cancer tissues.
authors.affiliation: Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany.
authors.forename: Turang E
authors.initials: TE
authors.lastname: Behbahani
authors.forename: Claudia
authors.initials: C
authors.lastname: Thierse
authors.forename: Claudia
authors.initials: C
authors.lastname: Baumann
authors.forename: Daniel
authors.initials: D
authors.lastname: Holl
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Alexander
authors.initials: A
authors.lastname: von Ruecker
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Hauser
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D066247:Receptor, ErbB-4; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D066247:Receptor, ErbB-4; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck