Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney

Wagener, Nina; Crnković-Mertens, Irena; Vetter, C; Macher-Göppinger, Stephan; Bedke, Jens; Gröne, Elisabeth F.; Zentgraf, H.; Pritsch, Maria; Hoppe‐Seyler, Karin; Buse, Stephan; Haferkamp, Axel; Autschbach, Frank; Hohenfellner, Markus; Hoppe‐Seyler, Felix

doi:10.1038/sj.bjc.6604028

Cited by 33 publications

(27 citation statements)

References 34 publications

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“…In the same year, it was reported that Livin-a and Livin-h were unexpectedly found to be different between renal cell carcinoma and normal kidney tissues. Besides, the results showed that even if cytoplasmic Livin was presented in both renal cell carcinoma and normal kidney tissues, nuclear Livin could only be detectable in renal cell carcinoma (46). Supporting his conclusion, Nedelcu et al successively identified that the nuclear localization of Livin was in parallel with a decreased overall survival in osteosarcoma patients (47).…”

Section: Validating Livin As a Potential Prognostic Markersupporting

confidence: 63%

Challenge and promise: roles for Livin in progression and therapy of cancer

Wang

Zhang²,

Liu

et al. 2008

Molecular Cancer Therapeutics

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Livin is a member of the inhibitors of apoptosis protein gene family, which is highly expressed in a variety of human neoplasms. Several studies have shown that down-regulation of Livin expression increases the apoptotic rate, reduces tumor growth potential, and sensitizes tumor cells to chemotherapeutic drugs. Furthermore, emerging data reveal that Livin fragments cleavaged by caspases restored paradoxical proapoptotic activity during the apoptotic process, suggesting that Livin cleavage will become a highly potent proapoptotic agent in the future. In this article, we review the current understanding of the versatile roles of Livin in the apoptotic cascade and exploit the promising approach to interfere with Livin as a novel strategy for cancer therapy. [Mol Cancer Ther 2008;7(12):3661 -9]

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Section: Validating Livin As a Potential Prognostic Markersupporting

confidence: 63%

Challenge and promise: roles for Livin in progression and therapy of cancer

Wang

Zhang²,

Liu

et al. 2008

Molecular Cancer Therapeutics

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“…6 24 ; mouse anti-p53 (BD Pharmingen), #554293, 1:500; rabbit anti-Survivin (Novus Biologicals, Littleton, CO), NB 500-201, 1:1,000; rabbit anti-TSG101 (Sigma-Aldrich), T5951, 1:500; goat anti-c-IAP1 (R&D Systems, Wiesbaden, Germany), AF8181, 1:1,000; and rabbit anti-XIAP (Cell Signaling, Danvers, MA), #2045, 1:1,000. The following HRP-conjugated secondary antibodies were applied: anti-mouse IgG (Promega, Madison, WI), W4021, 1:5,000; anti-rabbit IgG (Promega), W4011, 1:3,000; anti-chicken IgY (Promega), G1351, 1:2,500; anti-goat IgG (Promega), V8051, 1:3,000; and anti-rat IgG (Dianova, Hamburg, Germany), #112035003, 1:5,000.…”

Section: Immunoblottingmentioning

confidence: 99%

Silencing of human papillomavirus (HPV) E6/E7 oncogene expression affects both the contents and the amounts of extracellular microvesicles released from HPV‐positive cancer cells

Honegger

Leitz

Bulkescher

et al. 2013

Intl Journal of Cancer

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The human papillomavirus (HPV) E6/E7 oncogenes play a crucial role in the HPV-induced carcinogenesis. In this study, the authors investigated whether silencing of endogenous HPV E6/E7 expression may influence the contents or amounts of extracellular microvesicles (eMVs) released from HPV-positive cancer cells. It was found that eMVs secreted from HeLa cells are enriched for Survivin protein. RNA interference studies revealed that maintenance of both intracellular and microvesicular Survivin amounts was strongly dependent on continuous E6/E7 expression. This indicates that intracellular HPV activities are translated into visible alterations of protein contents in eMVs. Besides Survivin, eMVs from HeLa cells contain additional members of the inhibitor of apoptosis protein (IAP) family (XIAP, c-IAP1 and Livin). In contrast, no evidence for the presence of the HPV E6 and E7 oncoproteins in eMVs was obtained. Moreover, it was found that silencing of HPV E6/E7 expression led to a significant increase of exosomes-representing eMVs of endocytic origin-released from HeLa cells. This effect was associated with the reinduction of p53, stimulation of the p53 target genes TSAP6 and CHMP4C that can enhance exosome production and induction of senescence. Taken together, these results show that silencing of HPV E6/E7 oncogene expression profoundly affects both the composition and amounts of eMVs secreted by HPV-positive cancer cells. This indicates that HPVs can induce molecular signatures in eMVs that may affect intercellular communication and could be explored for diagnostic purposes.Specific types of human papillomaviruses (HPVs), such as HPV16 and HPV18, cause cervical cancer and are closely linked to the development of additional human malignancies in the oropharyngeal and anogenital regions. 1 The viral E6 and E7 oncoproteins are crucial both for the HPV-associated induction of transformation and for the maintenance of the tumorigenic phenotype of HPV-positive cervical cancer cells. 2,3 E6 and E7 dysregulate intracellular pathways involved in the control of cellular proliferation, apoptosis and genetic stability. For example, E6 induces the proteolytic degradation of the p53 tumor suppressor protein 4 and stimulates telomerase activity, 5 whereas E7 interferes with the activity of the retinoblastoma tumor suppressor protein, pRb, and other pocket proteins. 6 In contrast to the increasing understanding of the intracellular activities of the viral E6/E7 oncogenes, surprisingly little is known about possible effects on the intercellular communication of HPV-positive cancer cells.Extracellular microvesicles (eMVs) include exosomes that are small vesicles (50-100 nm in diameter) of endosomal origin secreted by a variety of cells, including tumor cells. 7 Exosomes have recently gained much interest in oncology, particularly due to three properties: (i) exosomes secreted from tumor cells can suppress the immune response toward the tumor, 8,9 (ii) tumor cell-derived exosomes can accelerate tumor growth and invasiveness by horizon...

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“…Andere Untersuchungen zeigten z. B., dass mittels anhand von immunhistochemischen Färbungen eines TMA mit 600 Gewebeproben von Nierenzellkarzinompatienten die Identifizierung von molekularbiologischen Markern und deren prognostischer Relevanz beim Nierenzellkarzinom möglich ist [19,20,21,22,23,24,25].…”

Section: Bisheriger Nutzen Der Urologischen Tumordatenbankunclassified