title: Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.
abstract: OBJECTIVE
  The EphA2 receptor tyrosine kinase is believed to play a role in tumor growth and metastasis. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers. The purpose of this work was to determine the expression of EphA2 and its ligand, Ephrin A-1, and E-cadherin in carcinoma of the urinary bladder, and determine EphA2 as a new target for therapy in bladder cancer.
  
  
  METHODS
  EphA2 mRNA and protein expression was investigated by reverse transcription-PCR and Western blot, respectively, in bladder cancer cell lines. In addition, the expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with different stages of urinary bladder cancer was determined by immunohistochemistry. Furthermore, the ability of Ephrin A-1 to inhibit growth of bladder cancer cells was also investigated using an adenoviral delivery system.
  
  
  RESULTS
  Western blot analysis showed high EphA2 expression in TCCSUP, T24, and UMUC-3 cell lines. In tissues, the staining intensity of EphA2 was less in normal urothelium but increased greatly in advancing stages of urothelial carcinoma (P < 0.05). Similarly, the staining intensity of Ephrin A-1 was low in normal tissues and high in cancerous tissues, but it was similar across the various stages of urothelial carcinoma (T(a)-T(4)). E-cadherin immunoreactivity decreased in urothelial cancer. Association of EphA2 and Ephrin A-1 expression was found to be significant between T(a) stage and T(1)-T(2) (P < 0.04) and T(a) and T(3)-T(4) stages (P < 0.0001). Adenovirus delivery of Ephrin A-1 inhibited proliferation of TCCSUP cells.
  
  
  CONCLUSIONS
  EphA2 may serve as a novel target for bladder cancer therapy.
authors.affiliation: Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47909, USA.
authors.forename: Shaji
authors.initials: S
authors.lastname: Abraham
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Knapp
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Paul W
authors.initials: PW
authors.lastname: Snyder
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Mittal
authors.forename: Dinesh S
authors.initials: DS
authors.lastname: Bangari
authors.forename: Michael
authors.initials: M
authors.lastname: Kinch
authors.forename: Lan
authors.initials: L
authors.lastname: Wu
authors.forename: Jay
authors.initials: J
authors.lastname: Dhariwal
authors.forename: Sulma I
authors.initials: SI
authors.lastname: Mohammed
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D036382:Ephrin-A1 / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D036104:Receptor, EphA2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D015820:Cadherins; D036382:Ephrin-A1; D012333:RNA, Messenger; D036104:Receptor, EphA2