The equilibrium of XIAP and Smac/DIABLO expression is gradually deranged during the development and progression of testicular germ cell tumours
2007
Kempkensteffen, Carsten | Jäger, Tobias | Bub, Johannes | Weikert, Steffen | Hinz, Stefan | Christoph, Frank | Krause, Hans | Schostak, Martin | Miller, Kurt | Schrader, Mark
Overexpression of the inhibitor of apoptosis protein (IAP) XIAP (BIRC4) and downregulation of its antagonist Smac/DIABLO (DIABLO) are associated with the onset and progression of various malignancies. In this study, real-time RT-PCR was used to quantify the mRNA expression of XIAP and Smac/DIABLO in normal testicular tissue (n = 19), testicular carcinoma in situ (CIS; n = 4), testicular seminomas (n = 64) and non-seminomatous germ cell tumours (NSGCT; n = 35). XIAP and Smac/DIABLO were commonly expressed in normal and malignant testicular tissue with no apparent differences in XIAP mRNA levels among the histologic subgroups. Smac/DIABLO levels, on the other hand, gradually decreased from normal testicular tissue to CIS and seminomas and finally to NSGCT (p < 0.001). An inverse trend was observed when calculating the XIAP-to-Smac/DIABLO ratio (p < 0.001). This ratio differed when comparing normal testicular tissue with CIS (p = 0.014), seminomas (p < 0.001) and NSGCT (p < 0.001) and when comparing seminomas with NSGCT (p = 0.002), whereas no such difference was observed between CIS and seminomas (p = 0.302). TGCT patients dichotomized by the overall median XIAP-to-Smac/DIABLO ratio were more likely to present with a high ratio in clinical stage (CS) III than in CS I or II (p = 0.034). These data indicate that the balance of mRNA expression between XIAP and Smac/DIABLO is altered in favour of antiapoptotic XIAP during the development and progression of TGCT. Thus the expression of proapoptotic Smac/DIABLO is lowest in NSGCT and stage III tumours.
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