Expression of splicing variants of the inhibitor of apoptosis livin in testicular germ cell tumors.
The inhibitor of apoptosis family member livin is expressed in several neoplasms but is absent in most benign tissues. Livin has therefore been evaluated as a diagnostic and prognostic marker and recently gained much attention as a target for tumor therapy. We evaluated the expression of livin splicing variants in 131 testicular germ cell tumors (TGCT) compared to 20 normal testicular tissue samples using dual-color real-time RT-PCR and Western blot analysis. Expression of livin beta was detected in 51.9% and expression of the alpha-variant in 28.2% of the TGCT specimens. None of the splicing variants could be detected in normal testicular tissue. Livin alpha was only expressed in combination with the beta-isoform, the respective expression levels being highly intercorrelated (Spearman's correlation coefficient: rho = 0.854). Livin expression was strongly related to TGCT differentiation but not to clinical tumor stage and patient age. The beta-variant was expressed in 67.5% of seminomas but only in 27.1% of nonseminomatous germ cell tumors (NSGCT). Expression of the alpha-variant was detected in 38.5% of seminomas and in 10.4% of NSGCT. Among NSGCT, livin expression was confined to embryonal carcinomas (EC) and mixed NSGCT exclusively consisting of EC and seminoma elements. Our findings suggest livin to be implicated in testicular tumorigenesis and to be related to the histological TGCT subtype. Considering that livin expression is restricted to malignant testicular tissue, it appears reasonable to conduct further investigations regarding its targeted inhibition in TGCT.
Department of Urology, Charité, University Medicine Berlin, Berlin, Germany. carsten.kempkensteffen@charite.de
Carsten
C
Kempkensteffen
Stefan
S
Hinz
Hans
H
Krause
Tobias
T
Jager
Jens
J
Köllermann
Steffen
S
Weikert
Frank
F
Christoph
Martin
M
Schostak
Kurt
K
Miller
Mark
M
Schrader
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D019154:Protein Splicing / Q000235:genetics*; D018239:Seminoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000166:cytology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms