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Identification of BIRC6 as a novel intervention target for neuroblastoma therapy
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| Zeitschriftentitel: | BMC Cancer |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | BMC Cancer, 12, 2012, 1 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Springer Science and Business Media LLC
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| Schlagwörter: |
| author_facet |
Lamers, Fieke Schild, Linda Koster, Jan Speleman, Frank Øra, Ingrid Westerhout, Ellen M van Sluis, Peter Versteeg, Rogier Caron, Huib N Molenaar, Jan J Lamers, Fieke Schild, Linda Koster, Jan Speleman, Frank Øra, Ingrid Westerhout, Ellen M van Sluis, Peter Versteeg, Rogier Caron, Huib N Molenaar, Jan J |
|---|---|
| author |
Lamers, Fieke Schild, Linda Koster, Jan Speleman, Frank Øra, Ingrid Westerhout, Ellen M van Sluis, Peter Versteeg, Rogier Caron, Huib N Molenaar, Jan J |
| spellingShingle |
Lamers, Fieke Schild, Linda Koster, Jan Speleman, Frank Øra, Ingrid Westerhout, Ellen M van Sluis, Peter Versteeg, Rogier Caron, Huib N Molenaar, Jan J BMC Cancer Identification of BIRC6 as a novel intervention target for neuroblastoma therapy Cancer Research Genetics Oncology |
| author_sort |
lamers, fieke |
| spelling |
Lamers, Fieke Schild, Linda Koster, Jan Speleman, Frank Øra, Ingrid Westerhout, Ellen M van Sluis, Peter Versteeg, Rogier Caron, Huib N Molenaar, Jan J 1471-2407 Springer Science and Business Media LLC Cancer Research Genetics Oncology http://dx.doi.org/10.1186/1471-2407-12-285 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Neuroblastoma are pediatric tumors of the sympathetic nervous system with a poor prognosis. Apoptosis is often deregulated in cancer cells, but only a few defects in apoptotic routes have been identified in neuroblastoma.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Here we investigated genomic aberrations affecting genes of the intrinsic apoptotic pathway in neuroblastoma. We analyzed DNA profiling data (CGH and SNP arrays) and mRNA expression data of 31 genes of the intrinsic apoptotic pathway in a dataset of 88 neuroblastoma tumors using the R2 bioinformatic platform (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://r2.amc.nl" ext-link-type="uri">http://r2.amc.nl</jats:ext-link>). BIRC6 was selected for further analysis as a tumor driving gene. Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays. In addition, DIABLO levels and interactions were investigated with immunofluorescence and co-immunoprecipitation.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>We observed frequent gain of the <jats:italic>BIRC6</jats:italic> gene on chromosome 2, which resulted in increased mRNA expression. BIRC6 is an inhibitor of apoptosis protein (IAP), that can bind and degrade the cytoplasmic fraction of the pro-apoptotic protein DIABLO. <jats:italic>DIABLO</jats:italic> mRNA expression was exceptionally high in neuroblastoma but the protein was only detected in the mitochondria. Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. Co-immunoprecipitation confirmed direct interaction between DIABLO and BIRC6 in neuroblastoma cell lines.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Our findings indicate that BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO. BIRC6 inhibition may therefore provide a means for therapeutic intervention in neuroblastoma.</jats:p> </jats:sec> Identification of BIRC6 as a novel intervention target for neuroblastoma therapy BMC Cancer |
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10.1186/1471-2407-12-285 |
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Springer Science and Business Media LLC, 2012 |
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Springer Science and Business Media LLC, 2012 |
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2012 |
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| title |
Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_unstemmed |
Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_full |
Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_fullStr |
Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_full_unstemmed |
Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_short |
Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_sort |
identification of birc6 as a novel intervention target for neuroblastoma therapy |
| topic |
Cancer Research Genetics Oncology |
| url |
http://dx.doi.org/10.1186/1471-2407-12-285 |
| publishDate |
2012 |
| physical |
|
| description |
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>Neuroblastoma are pediatric tumors of the sympathetic nervous system with a poor prognosis. Apoptosis is often deregulated in cancer cells, but only a few defects in apoptotic routes have been identified in neuroblastoma.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>Here we investigated genomic aberrations affecting genes of the intrinsic apoptotic pathway in neuroblastoma. We analyzed DNA profiling data (CGH and SNP arrays) and mRNA expression data of 31 genes of the intrinsic apoptotic pathway in a dataset of 88 neuroblastoma tumors using the R2 bioinformatic platform (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://r2.amc.nl" ext-link-type="uri">http://r2.amc.nl</jats:ext-link>). BIRC6 was selected for further analysis as a tumor driving gene. Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays. In addition, DIABLO levels and interactions were investigated with immunofluorescence and co-immunoprecipitation.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>We observed frequent gain of the <jats:italic>BIRC6</jats:italic> gene on chromosome 2, which resulted in increased mRNA expression. BIRC6 is an inhibitor of apoptosis protein (IAP), that can bind and degrade the cytoplasmic fraction of the pro-apoptotic protein DIABLO. <jats:italic>DIABLO</jats:italic> mRNA expression was exceptionally high in neuroblastoma but the protein was only detected in the mitochondria. Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. Co-immunoprecipitation confirmed direct interaction between DIABLO and BIRC6 in neuroblastoma cell lines.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>Our findings indicate that BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO. BIRC6 inhibition may therefore provide a means for therapeutic intervention in neuroblastoma.</jats:p>
</jats:sec> |
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| author | Lamers, Fieke, Schild, Linda, Koster, Jan, Speleman, Frank, Øra, Ingrid, Westerhout, Ellen M, van Sluis, Peter, Versteeg, Rogier, Caron, Huib N, Molenaar, Jan J |
| author_facet | Lamers, Fieke, Schild, Linda, Koster, Jan, Speleman, Frank, Øra, Ingrid, Westerhout, Ellen M, van Sluis, Peter, Versteeg, Rogier, Caron, Huib N, Molenaar, Jan J, Lamers, Fieke, Schild, Linda, Koster, Jan, Speleman, Frank, Øra, Ingrid, Westerhout, Ellen M, van Sluis, Peter, Versteeg, Rogier, Caron, Huib N, Molenaar, Jan J |
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| description | <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Neuroblastoma are pediatric tumors of the sympathetic nervous system with a poor prognosis. Apoptosis is often deregulated in cancer cells, but only a few defects in apoptotic routes have been identified in neuroblastoma.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Here we investigated genomic aberrations affecting genes of the intrinsic apoptotic pathway in neuroblastoma. We analyzed DNA profiling data (CGH and SNP arrays) and mRNA expression data of 31 genes of the intrinsic apoptotic pathway in a dataset of 88 neuroblastoma tumors using the R2 bioinformatic platform (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://r2.amc.nl" ext-link-type="uri">http://r2.amc.nl</jats:ext-link>). BIRC6 was selected for further analysis as a tumor driving gene. Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays. In addition, DIABLO levels and interactions were investigated with immunofluorescence and co-immunoprecipitation.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>We observed frequent gain of the <jats:italic>BIRC6</jats:italic> gene on chromosome 2, which resulted in increased mRNA expression. BIRC6 is an inhibitor of apoptosis protein (IAP), that can bind and degrade the cytoplasmic fraction of the pro-apoptotic protein DIABLO. <jats:italic>DIABLO</jats:italic> mRNA expression was exceptionally high in neuroblastoma but the protein was only detected in the mitochondria. Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. Co-immunoprecipitation confirmed direct interaction between DIABLO and BIRC6 in neuroblastoma cell lines.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Our findings indicate that BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO. BIRC6 inhibition may therefore provide a means for therapeutic intervention in neuroblastoma.</jats:p> </jats:sec> |
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| institution | DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1 |
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| spelling | Lamers, Fieke Schild, Linda Koster, Jan Speleman, Frank Øra, Ingrid Westerhout, Ellen M van Sluis, Peter Versteeg, Rogier Caron, Huib N Molenaar, Jan J 1471-2407 Springer Science and Business Media LLC Cancer Research Genetics Oncology http://dx.doi.org/10.1186/1471-2407-12-285 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Neuroblastoma are pediatric tumors of the sympathetic nervous system with a poor prognosis. Apoptosis is often deregulated in cancer cells, but only a few defects in apoptotic routes have been identified in neuroblastoma.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Here we investigated genomic aberrations affecting genes of the intrinsic apoptotic pathway in neuroblastoma. We analyzed DNA profiling data (CGH and SNP arrays) and mRNA expression data of 31 genes of the intrinsic apoptotic pathway in a dataset of 88 neuroblastoma tumors using the R2 bioinformatic platform (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://r2.amc.nl" ext-link-type="uri">http://r2.amc.nl</jats:ext-link>). BIRC6 was selected for further analysis as a tumor driving gene. Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays. In addition, DIABLO levels and interactions were investigated with immunofluorescence and co-immunoprecipitation.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>We observed frequent gain of the <jats:italic>BIRC6</jats:italic> gene on chromosome 2, which resulted in increased mRNA expression. BIRC6 is an inhibitor of apoptosis protein (IAP), that can bind and degrade the cytoplasmic fraction of the pro-apoptotic protein DIABLO. <jats:italic>DIABLO</jats:italic> mRNA expression was exceptionally high in neuroblastoma but the protein was only detected in the mitochondria. Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. Co-immunoprecipitation confirmed direct interaction between DIABLO and BIRC6 in neuroblastoma cell lines.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Our findings indicate that BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO. BIRC6 inhibition may therefore provide a means for therapeutic intervention in neuroblastoma.</jats:p> </jats:sec> Identification of BIRC6 as a novel intervention target for neuroblastoma therapy BMC Cancer |
| spellingShingle | Lamers, Fieke, Schild, Linda, Koster, Jan, Speleman, Frank, Øra, Ingrid, Westerhout, Ellen M, van Sluis, Peter, Versteeg, Rogier, Caron, Huib N, Molenaar, Jan J, BMC Cancer, Identification of BIRC6 as a novel intervention target for neuroblastoma therapy, Cancer Research, Genetics, Oncology |
| title | Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_full | Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_fullStr | Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_full_unstemmed | Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_short | Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| title_sort | identification of birc6 as a novel intervention target for neuroblastoma therapy |
| title_unstemmed | Identification of BIRC6 as a novel intervention target for neuroblastoma therapy |
| topic | Cancer Research, Genetics, Oncology |
| url | http://dx.doi.org/10.1186/1471-2407-12-285 |