title: The equilibrium of XIAP and Smac/DIABLO expression is gradually deranged during the development and progression of testicular germ cell tumours.
abstract: 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.
authors.affiliation: Department of Urology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. carsten.kempkenstefen@charite.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Kempkensteffen
authors.forename: Tobias
authors.initials: T
authors.lastname: Jäger
authors.forename: Johannes
authors.initials: J
authors.lastname: Bub
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Stefan
authors.initials: S
authors.lastname: Hinz
authors.forename: Frank
authors.initials: F
authors.lastname: Christoph
authors.forename: Hans
authors.initials: H
authors.lastname: Krause
authors.forename: Martin
authors.initials: M
authors.lastname: Schostak
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Mark
authors.initials: M
authors.lastname: Schrader
mesh_terms: D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D017931:DNA Primers; D018450:Disease Progression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human