Expression of endothelin-1 and endothelin-A and -B receptors in invasive bladder cancer.
Overexpression of endothelin-1, endothelin-A- and endothelin-B-receptors has been shown in various human tumors. To assess the role of the ET-axis in bladder cancer, we analyzed its expression in tumor specimens and bladder cancer cell lines. Samples were obtained by radical cystectomy at two urologic institutions. ET-axis expression was investigated by reverse-transcription polymerase chain reaction (RT-PCR) (n=22) and immunohistochemistry (n=42). Additionally, four bladder cancer cell lines were analyzed. RT-PCR analysis for the ET-axis showed positive signals in the majority of cDNA probes. Signals for endothelin-1 (ET-1), endothelin-A-receptor (ET(A)R) and endothelin-B-receptor (ET(B)R), as identified semiquantitatively and by densitometry, were found in 22, 22 and 15 of 22 cases, respectively. Immunohistochemistry revealed expression of ET-1, ET(A)- and ET(B)-receptor in 18, 29 and 37 of the 42 cases, respectively, whereas normal urothelium was negative. All cell lines expressed ET-1, and all but the RT-112 cell line produced ETAR, whereas no cell line expressed ET(B)R. The identification of the ET-axis at the mRNA and protein level in the majority of bladder tumor samples suggests a role in the carcinogenesis of bladder cancer. Further studies on regulation of the ET-axis and the future use of selective ET(A)-receptor inhibitors for targeted molecular therapy in bladder cancer are in progress.
Wülfing
Christian
C
Department of Urology, Institute of Pathology, University of Münster, Germany. wulfing@uni-muenster.de
Eltze
Elke
E
Piechota
Hansjürgen
H
Abol-Enein
Hassan
H
Wülfing
Pia
P
Bode
Marc-Eric
ME
Hertle
Lothar
L
Sievert
Karl-Dietrich
KD
D000328:Adult; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B