Quantification of survivin mRNA in testes of infertile patients and in testicular germ cell tumours: high levels of expression associated with normal spermatogenesis

Weikert, Steffen; Schrader, Mark; Christoph, Frank; Schulze, Wolfgang; Krause, Hans; Müller, Markus; Miller, Kurt

doi:10.1111/j.1365-2605.2005.00549.x

Cited by 12 publications

(8 citation statements)

References 24 publications

(58 reference statements)

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“…The hypothesis has been put forward that NSGCT originate through the reprogramming of pluripotent gonocytes to carcinoma in situ cells which differentiate into seminoma or EC cells which may again differentiate into somatic and extraembryonal elements [34] . Our findings are on principle in line with this model and may indicate livin expression to relate to the histologic tumor subtype, as previously shown for survivin, too [35,36] . To further examine the role of livin in TGCT development and differentiation, subsequent studies including samples of carcinomas in situ and additional markers of TGCT differentiation are necessary.…”

Section: Discussionsupporting

confidence: 77%

Expression of Splicing Variants of the Inhibitor of Apoptosis Livin in Testicular Germ Cell Tumors

Kempkensteffen¹,

Hinz²,

Krause³

et al. 2008

Tumor Biol

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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 β was detected in 51.9% and expression of the α-variant in 28.2% of the TGCT specimens. None of the splicing variants could be detected in normal testicular tissue. Livin α was only expressed in combination with the β-isoform, the respective expression levels being highly intercorrelated (Spearman’s correlation coefficient: ρ = 0.854). Livin expression was strongly related to TGCT differentiation but not to clinical tumor stage and patient age. The β-variant was expressed in 67.5% of seminomas but only in 27.1% of nonseminomatous germ cell tumors (NSGCT). Expression of the α-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.

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Section: Discussionsupporting

confidence: 77%

Expression of Splicing Variants of the Inhibitor of Apoptosis Livin in Testicular Germ Cell Tumors

Kempkensteffen¹,

Hinz²,

Krause³

et al. 2008

Tumor Biol

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“…LTR promoters may be particularly responsive to upregulation by cellular stresses since it has been shown that activation of human and mouse ERV LTRs can occur following stresses such as viral infection [54–56] and UV irradiation [57,58]. Various IAPs are expressed in human [59,60], mouse [61], and rat [62,63] germ cells or their progenitors, and it has been reported that Naip expression plays a role in mouse oocyte viability [61]. Although nothing is known about a potential NAIP stress response in the germ line, it has been demonstrated that NAIP mRNA and protein is upregulated in neurons following ischemic stress [64].…”

Section: Discussionmentioning

confidence: 99%

Repeated Recruitment of LTR Retrotransposons as Promoters by the Anti-Apoptotic Locus NAIP during Mammalian Evolution

et al. 2007

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Neuronal apoptosis inhibitory protein (NAIP, also known as BIRC1) is a member of the conserved inhibitor of apoptosis protein (IAP) family. Lineage-specific rearrangements and expansions of this locus have yielded different copy numbers among primates and rodents, with human retaining a single functional copy and mouse possessing several copies, depending on the strain. Roles for this gene in disease have been documented, but little is known about transcriptional regulation of NAIP. We show here that NAIP has multiple promoters sharing no similarity between human and rodents. Moreover, we demonstrate that multiple, domesticated long terminal repeats (LTRs) of endogenous retroviral elements provide NAIP promoter function in human, mouse, and rat. In human, an LTR serves as a tissue-specific promoter, active primarily in testis. However, in rodents, our evidence indicates that an ancestral LTR common to all rodent genes is the major, constitutive promoter for these genes, and that a second LTR found in two of the mouse genes is a minor promoter. Thus, independently acquired LTRs have assumed regulatory roles for orthologous genes, a remarkable evolutionary scenario. We also demonstrate that 5′ flanking regions of IAP family genes as a group, in both human and mouse are enriched for LTR insertions compared to average genes. We propose several potential explanations for these findings, including a hypothesis that recruitment of LTRs near NAIP or other IAP genes may represent a host-cell adaptation to modulate apoptotic responses.

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“…The studies of Weikert et al [5] have shown that testicular survivin levels in infertile patients were related inversely to the severity of spermatogenic failure (p ! 0.001), with a lack of expression in most specimens with premeiotic spermatogenic arrest and in all those with germ cell aplasia [10,11] . Another study by Roshdy and Mostafa [12] showed that seminal survivin was significantly high in fertile control males in comparison with oligo-asthenozoospermic and nonobstructive azoospermia patients.…”

Section: Discussionmentioning

confidence: 99%

Survivin Downregulation Is Associated with Vasectomy-Induced Spermatogenic Damage and Apoptosis

Al‐Maghrebi¹,

Kehinde²,

Anim

2011

Med Princ Pract

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Objective: To evaluate the expression of the apoptotic genes survivin, Bax and Bcl-2 in vasectomized rabbits and to determine their relation with vasectomy-induced spermatogenic impairment and germ cell apoptosis. Materials and Methods: Twelve adult rabbits (6–12 months old) were divided into three groups: sham control, unilateral vasectomy or bilateral vasectomy. Six months after vasectomy, testicular tissue was analyzed for germ cell apoptosis and DNA fragmentation by the TUNEL assay and gel electrophoresis, respectively. Spermatogenesis was assessed using the Johnsen score. The relative gene expression of survivin, Bax and Bcl-2 was measured using reverse transcription followed by real-time PCR. Results: Compared to sham animals, a significant decrease in testicular survivin mRNA levels was measured in the two vasectomy animal groups (p < 0.05). This was accompanied by a significant increase in the Bax:Bcl-2 ratio in the vasectomized animals (p < 0.05). In addition, these data showed positive correlation with enhanced apoptotic index, damage to spermatogenesis and DNA fragmentation after vasectomy. Conclusion: These findings demonstrate that vasectomy-induced damage to spermatogenesis due to testicular apoptosis may be associated with survivin downregulation and Bax overexpression.

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Quantification of survivin mRNA in testes of infertile patients and in testicular germ cell tumours: high levels of expression associated with normal spermatogenesis

Cited by 12 publications

References 24 publications

Expression of Splicing Variants of the Inhibitor of Apoptosis Livin in Testicular Germ Cell Tumors

Expression of Splicing Variants of the Inhibitor of Apoptosis Livin in Testicular Germ Cell Tumors

Repeated Recruitment of LTR Retrotransposons as Promoters by the Anti-Apoptotic Locus NAIP during Mammalian Evolution

Survivin Downregulation Is Associated with Vasectomy-Induced Spermatogenic Damage and Apoptosis

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