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.
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Authors | Carsten Kempkensteffen, Tobias Jäger, Johannes Bub, Steffen Weikert, Stefan Hinz, Frank Christoph, Hans Krause, Martin Schostak, Kurt Miller, Mark Schrader |
Journal | International journal of andrology
(Int J Androl)
Vol. 30
Issue 5
Pg. 476-83
(Oct 2007)
ISSN: 0105-6263 [Print] England |
PMID | 17298543
(Publication Type: Journal Article)
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Chemical References |
- Apoptosis Regulatory Proteins
- DIABLO protein, human
- DNA Primers
- Intracellular Signaling Peptides and Proteins
- Mitochondrial Proteins
- X-Linked Inhibitor of Apoptosis Protein
- XIAP protein, human
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Topics |
- Apoptosis Regulatory Proteins
- Base Sequence
- DNA Primers
- Disease Progression
- Humans
- Intracellular Signaling Peptides and Proteins
(genetics, metabolism)
- Male
- Mitochondrial Proteins
(genetics, metabolism)
- Neoplasms, Germ Cell and Embryonal
(metabolism, pathology)
- Reverse Transcriptase Polymerase Chain Reaction
- Testicular Neoplasms
(metabolism, pathology)
- X-Linked Inhibitor of Apoptosis Protein
(genetics, metabolism)
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