Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.
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.
Abraham
Shaji
S
Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47909, USA.
Knapp
Deborah W
DW
Cheng
Liang
L
Snyder
Paul W
PW
Mittal
Suresh K
SK
Bangari
Dinesh S
DS
Kinch
Michael
M
Wu
Lan
L
Dhariwal
Jay
J
Mohammed
Sulma I
SI
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
D015820:Cadherins; D036382:Ephrin-A1; D012333:RNA, Messenger; D036104:Receptor, EphA2