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Irena Crnkovicmertens - One of the best experts on this subject based on the ideXlab platform.
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expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non tumorous adult kidney
British Journal of Cancer, 2007Co-Authors: Irena Crnkovicmertens, Nina Wagener, C Vetter, Stephan Machergoppinger, Jens Bedke, Elisabeth Grone, Hanswalter Zentgraf, Maria Pritsch, Karin HoppeseylerAbstract:The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that Livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of Livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of Livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that Livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms α and β were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of Livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific.
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the anti apoptotic Livin gene is an important determinant for the apoptotic resistance of non small cell lung cancer cells
Lung Cancer, 2006Co-Authors: Irena Crnkovicmertens, Julia Semzow, Karin Butz, Thomas Muley, M Meister, Bettina Hartenstein, Felix HoppeseylerAbstract:Cancer cells are typically characterized by increased resistance towards apoptosis. Livin (alternatively called ML-IAP or KIAP) is an anti-apoptotic protein which is expressed in several cancer forms. Using real-time reverse transcription-polymerase chain reaction (RT-PCR), we confirmed Livin expression in a significant portion of non-small cell lung cancer (NSCLC) tissue samples and, in addition, detected Livin expression in a number of NSCLC cell lines. In order to elucidate whether Livin contributes to the apoptotic resistance of lung cancer cells, we silenced endogenous Livin expression in a panel of cancer-derived NSCLC cell lines by RNA interference (RNAi). We observed that the targeted inhibition of Livin strongly sensitized NSCLC cells to different pro-apoptotic stimuli, such as UV-irradiation or the chemotherapeutic drug etoposide. In addition, long-term silencing of Livin blocked the outgrowth of NSCLC cells in colony formation assays. These effects of small interfering (si)RNA were specific for Livin-expressing tumor cells. Our results indicate that Livin is an important contributor to the apoptosis resistance of NSCLC cells and may serve as a novel molecular target for therapeutic inhibition in NSCLC.
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isoform specific silencing of the Livin gene by rna interference defines Livin β as key mediator of apoptosis inhibition in hela cells
Journal of Molecular Medicine, 2006Co-Authors: Irena Crnkovicmertens, Julia Semzow, Felix Hoppeseyler, Karin ButzAbstract:Livin (alternatively called ML-IAP or KIAP) is a cancer-associated member of the antiapoptotic inhibitor of apoptosis protein family. Two splicing variants of Livin, designated Livin α and Livin β, have been identified. The significance of these isoforms for Livin-mediated apoptosis inhibition is largely unclear. Using an isoform-specific RNA interference (RNAi) strategy, we silenced endogenous Livin expression in HeLa cells. We found that the targeted inhibition of Livin β, but not of Livin α, blocked the growth of HeLa cells in clonogenic survival assays. In addition, silencing of Livin β, but not of Livin α, sensitized HeLa cells to different proapoptotic stimuli such as UV irradiation, tumor necrosis factor α, or etoposide. These events were linked to activation of caspase-3 and increased poly(ADP-ribose) polymerase cleavage, specifically upon silencing of Livin β. The proapoptotic sensitization of HeLa cells upon RNAi-mediated silencing of the endogenous Livin gene was specifically reverted by ectopic expression of Livin β but not of Livin α. We conclude that the Livin β isoform plays the key role for the antiapoptotic protection of HeLa cells by the Livin gene. Our results show that the Livin isoforms can strongly differ in their functional significance for the antiapoptotic resistance of tumor cells. Studies evaluating Livin as a novel diagnostic and prognostic tumor marker should benefit from isoform-specific expression analyses.
Xishuang Song - One of the best experts on this subject based on the ideXlab platform.
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Livin expression may be regulated by mir 198 in human prostate cancer cell lines
European Journal of Cancer, 2013Co-Authors: Deyong Yang, Jianing Zhang, Xiaochi Chen, Feng Yue, Yanjie Guo, Feng Chen, Xishuang SongAbstract:Abstract Livin has been recently described as an inhibitor of apoptosis, which is established to be associated with a variety of cancers. Metastatic prostate cancer cell line DU145 expresses high level of Livin mRNA yet low level of its protein. Thus, we hypothesised that Livin was regulated by some miRNAs in prostate cancer cells. Livin mRNA and protein expression were investigated by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. Hairpin RT-PCR was performed to analyse suspected miRNAs. Livin 3′-untranslated region (3′-UTR) wild type and mutant dual-luciferase reporter vectors were constructed. The miRNAs targeting Livin were predicted by the online software – TargetScan and miRBase, and then validated by dual luciferase reporter gene assay. We found that post-transcriptional inhibition of Livin occurred in DU145 cells, assumedly due to the miRNA pathway. Among 6 candidate miRNAs, miR-198 expression was identified to be negatively correlated with Livin expression level in some prostate cancer cell lines. Further study revealed miR-198-mediated repression of Livin expression. Therefore, the regulation of Livin expression may involve miR-198 in prostate cancer cell lines.
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Livin regulates prostate cancer cell invasion by impacting the nf κb signaling pathway and the expression of fn and cxcr4
Iubmb Life, 2012Co-Authors: Feng Chen, Deyong Yang, Xiangyu Che, Xiaochi Chen, Jianbo Wang, Zhiwei Zhang, Shujing Wang, Xishuang SongAbstract:Prostate cancer (PCa) has the second highest mortality rate of all tumor-related diseases for males in Western countries, and the incidence of PCa in China is increasing. Previous studies have proven that inhibitor of apoptosis proteins (IAPs) can regulate tumor cell invasion and metastasis. Livin is the most recently identified IAP. Our previous study showed that Livin might play an important role in the initiation of human PCa and that Livin-α might promote cell proliferation by regulating the G1–S cell cycle transition. However, whether Livin, as an IAP, can regulate the invasive ability of PCa cells remains unknown. In this study, we found that the expression of Livin was higher in metastatic PCa tissues than in nonmetastatic tissues and that the expression of Livin was downregulated/upregulated by small interfering RNA/vector, which could inhibit/promote PC-3/LNCaP cell invasion. This action was related to the impact of Livin on nuclear factor-κB (NF-κB) and its downstream signaling pathway, including FN and CXCR4. Together, our findings suggested that Livin might regulate tumor cell invasion in PCa directly, and that Livin might be an ideal candidate for preventing tumor cell invasion. © 2012 IUBMB IUBMB Life, 2012
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Livin α promotes cell proliferation by regulating g1 s cell cycle transition in prostate cancer
The Prostate, 2011Co-Authors: Xishuang Song, Deyong Yang, Jianing Zhang, Xiangyu Che, Xiaochi Chen, Jianbo Wang, Zhiwei ZhangAbstract:BACKGROUND Prostate cancer is the third most common cancer and the second leading cause of cancer death for males in US. Livin has recently been described as a cancer-associated member of inhibitor of apoptosis proteins family, highly expressed in prostate cancer. Livin gene encodes two splicing variants, termed Livin-α and Livin-β. We hypothesized that deregulation of proliferation could be due in part to Livin expression. METHODS Pathological analysis of Livin was performed in 20 prostate cancer tissues and 5 benign prostatic hyperplasia tissues. The expression of Livin isoforms was also investigated by Western blot in prostate cancer cell lines LNCaP and PC3. The role of Livin-α in vitro was further studied. Using Livin-α knockdown and overexpression models, cell cycle analysis, Ki-67 immunocytostaining, and MTT assay were performed respectively. RESULTS Livin expression positive ratio was shown to be 5.4%, 23.6%, 52.4%, 73.4% in benign prostatic hyperplasia, low, medium, and high grade of prostate cancer respectively, and Livin was positively correlated with clinical pathological grades of prostate cancer. Livin-α was expressed in both LNCaP and PC3; meanwhile; Livin-β was only detected in the PC3. Livin-α siRNA not only resulted in G1-S cell cycle arrest, but also strongly correlated with the descended proliferation index and survival rate in LNCaP. In comparison, overexpression of Livin-α resulted in an accelerated S phase entry combined with elevated proliferation index and survival in LNCaP. CONCLUSIONS Livin-α may promote cell proliferation by regulating G1-S cell cycle transition and possibly play an important part in initiation of prostate cancer. Prostate 71: 42–51, 2011. © 2010 Wiley-Liss, Inc.
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suppression of Livin gene expression by sirna leads to growth inhibition and apoptosis induction in human bladder cancer t24 cells
Bioscience Biotechnology and Biochemistry, 2010Co-Authors: Deyong Yang, Xishuang Song, Jianing Zhang, Xiangyu Che, Jianbo Wang, Zhiwei Zhang, Y E Lin, Shujing Wang, Li-na WangAbstract:Apoptosis deficiency is a hallmark of many cancer cells. Functional suppression of specific antiapoptotic factors might provide a feasible strategy in cancer gene therapy. Livin, the latest found inhibitor of apoptosis protein (IAP) family member, plays important role in cell growth and apoptosis. It has been reported that Livin is highly expressed in bladder cancer tissues. In this study, we found that, unlike other cancer cell lines, there was only Livin-α not Livin-β expression in bladder cancer cell lines. We further investigated the effects of Livin knockdown on human bladder cancer T24 cell growth and apoptosis. We found that small interfering RNA (siRNA) mediated Livin suppression significantly inhibited T24 cell proliferation and colony formation ability. Livin knockdown dramatically increased the T24 cell apoptotic rate in response to different proapoptotic stimuli, such as Mitomycin and TNF-alpha, and this was associated with caspase-3 and caspase-9 activation. These results suggest that Livin knockdown can inhibit cell growth and increase sensitivity to apoptotic stimuli, and might serve as a potent target in bladder cancer gene therapy.
Yihan Chen - One of the best experts on this subject based on the ideXlab platform.
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vegf stimulation enhances Livin protein synthesis through mtor signaling
Journal of Cellular Biochemistry, 2010Co-Authors: Biao Yan, Men Kong, Shi Chen, Yihan ChenAbstract:Livin is a member of inhibitors of apoptosis proteins (IAPs) and overexpressed in transformed cells and several cancers. Although strategies to decrease Livin levels have been conducted for rational cancer therapy, the molecular mechanism controlling Livin expression in tumors has not been completely elucidated. Here, we show that vascular endothelial growth factor (VEGF) stimulation can increase Livin expression in HeLa cells or SK-MEL-28 cells. This response is independent of de novo gene transcription or changes in mRNA expression but occurs at protein expression levels. VEGF stimulation results in mTOR signaling activation which changes the phosphorylation status of 4E-BP1, the downstream of mTOR signaling, and ultimately contributes to the translation initiation of Livin protein. Livin silencing, Rapamycin alone or in combination with cytotoxic agent can reduce Livin protein levels, and decrease cells viability. Thus, ablation of Livin translation contributes to remove an anti-apoptotic mechanism potentially contributing to aggressive tumor behavior. Pharmacologic inhibition of VEGF/mTOR/Livin signaling may provide a novel strategy for cancer treatment.
Nina Wagener - One of the best experts on this subject based on the ideXlab platform.
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expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non tumorous adult kidney
British Journal of Cancer, 2007Co-Authors: Irena Crnkovicmertens, Nina Wagener, C Vetter, Stephan Machergoppinger, Jens Bedke, Elisabeth Grone, Hanswalter Zentgraf, Maria Pritsch, Karin HoppeseylerAbstract:The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that Livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of Livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of Livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that Livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms α and β were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of Livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific.
Biao Yan - One of the best experts on this subject based on the ideXlab platform.
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Research progress on Livin protein: an inhibitor of apoptosis.
Molecular and cellular biochemistry, 2011Co-Authors: Biao YanAbstract:Livin is a member of the inhibitors of apoptosis (IAP) family, which plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Abnormal Livin expression is sometimes detected during the process of cancer formation and/or progression. Thus, Livin research may provide an opportunity for the development of potential therapy for Livin-relevant cancers. In this review, we introduce Livin structure, biological function, and its role in cancer formation and progression and the possible interventions for cancer therapy.
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vegf stimulation enhances Livin protein synthesis through mtor signaling
Journal of Cellular Biochemistry, 2010Co-Authors: Biao Yan, Men Kong, Shi Chen, Yihan ChenAbstract:Livin is a member of inhibitors of apoptosis proteins (IAPs) and overexpressed in transformed cells and several cancers. Although strategies to decrease Livin levels have been conducted for rational cancer therapy, the molecular mechanism controlling Livin expression in tumors has not been completely elucidated. Here, we show that vascular endothelial growth factor (VEGF) stimulation can increase Livin expression in HeLa cells or SK-MEL-28 cells. This response is independent of de novo gene transcription or changes in mRNA expression but occurs at protein expression levels. VEGF stimulation results in mTOR signaling activation which changes the phosphorylation status of 4E-BP1, the downstream of mTOR signaling, and ultimately contributes to the translation initiation of Livin protein. Livin silencing, Rapamycin alone or in combination with cytotoxic agent can reduce Livin protein levels, and decrease cells viability. Thus, ablation of Livin translation contributes to remove an anti-apoptotic mechanism potentially contributing to aggressive tumor behavior. Pharmacologic inhibition of VEGF/mTOR/Livin signaling may provide a novel strategy for cancer treatment.