Differential Signature of the Centrosomal MARK4 Isoforms in Glioma
Background: MAP/microtubule affinity-regulating kinase 4 (MARK4) is a serine-threonine kinase expressed in two spliced isoforms, MARK4L and MARK4S, of which MARK4L is a candidate for a role in neoplastic transformation. Methods: We performed mutation analysis to identify sequence alterations possibl...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.3233/ACP-2011-0031 |
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| author | Ivana Magnani Chiara Novielli Laura Fontana Silvia Tabano Davide Rovina Ramona F. Moroni Dario Bauer Stefania Mazzoleni Elisa A. Colombo Gabriella Tedeschi Laura Monti Giovanni Porta Silvano Bosari Carolina Frassoni Rossella Galli Lorenzo Bello Lidia Larizza |
| author_facet | Ivana Magnani Chiara Novielli Laura Fontana Silvia Tabano Davide Rovina Ramona F. Moroni Dario Bauer Stefania Mazzoleni Elisa A. Colombo Gabriella Tedeschi Laura Monti Giovanni Porta Silvano Bosari Carolina Frassoni Rossella Galli Lorenzo Bello Lidia Larizza |
| author_sort | Ivana Magnani |
| collection | DOAJ |
| description | Background: MAP/microtubule affinity-regulating kinase 4 (MARK4) is a serine-threonine kinase expressed in two spliced isoforms, MARK4L and MARK4S, of which MARK4L is a candidate for a role in neoplastic transformation. Methods: We performed mutation analysis to identify sequence alterations possibly affecting MARK4 expression. We then investigated the MARK4L and MARK4S expression profile in 21 glioma cell lines and 36 tissues of different malignancy grades, glioblastoma-derived cancer stem cells (GBM CSCs) and mouse neural stem cells (NSCs) by real-time PCR, immunoblotting and immunohistochemistry. We also analyzed the sub-cellular localisation of MARK4 isoforms in glioma and normal cell lines by immunofluorescence. Results: Mutation analysis rules out sequence variations as the cause of the altered MARK4 expression in glioma. Expression profiling confirms that MARK4L is the predominant isoform, whereas MARK4S levels are significantly decreased in comparison and show an inverse correlation with tumour grade. A high MARK4L/MARK4S ratio also characterizes undifferentiated cells, such as GBM CSCs and NSCs. Accordingly, only MARK4L is expressed in brain neurogenic regions. Moreover, while both MARK4 isoforms are localised to the centrosome and midbody in glioma and normal cells, the L isoform exhibits an additional nucleolar localisation in tumour cells. Conclusions: The observed switch towards MARK4L suggests that the balance between the MARK4 isoforms is carefully guarded during neural differentiation but may be subverted in gliomagenesis. Moreover, the MARK4L nucleolar localisation in tumour cells features this MARK4 isoform as a nucleolus-associated tumour marker. |
| format | Article |
| id | doaj-art-3ecf17df987948d4be7f551ce0a409e5 |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-3ecf17df987948d4be7f551ce0a409e52025-02-03T01:26:38ZengWileyAnalytical Cellular Pathology2210-71772210-71852011-01-0134631933810.3233/ACP-2011-0031Differential Signature of the Centrosomal MARK4 Isoforms in GliomaIvana Magnani0Chiara Novielli1Laura Fontana2Silvia Tabano3Davide Rovina4Ramona F. Moroni5Dario Bauer6Stefania Mazzoleni7Elisa A. Colombo8Gabriella Tedeschi9Laura Monti10Giovanni Porta11Silvano Bosari12Carolina Frassoni13Rossella Galli14Lorenzo Bello15Lidia Larizza16Department of Medicine, Surgery and Dentistry, Ospedale San Paolo, Medical Genetics, Università degli studi di Milano, Milan, ItalyDepartment of Medicine, Surgery and Dentistry, Ospedale San Paolo, Medical Genetics, Università degli studi di Milano, Milan, ItalyDepartment of Medicine, Surgery and Dentistry, Ospedale San Paolo, Medical Genetics, Università degli studi di Milano, Milan, ItalyDepartment of Medicine, Surgery and Dentistry, Ospedale San Paolo, Medical Genetics, Università degli studi di Milano, Milan, ItalyDepartment of Medicine, Surgery and Dentistry, Ospedale San Paolo, Medical Genetics, Università degli studi di Milano, Milan, ItalyUnit of Clinical Epileptology and Experimental Neurophysiology, Fondazione I.R.C.C.S. Istituto Neurologico “C. Besta”, Milan, ItalyDepartment of Medicine, Surgery and Dentistry, Pathology Unit, Ospedale San Paolo, Università degli studi di Milano, and Fondazione IRCCS Ca' Granda, Pathology Unit, Ospedale Maggiore Policlinico, Milan, ItalyNeural Stem Cell Biology Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, ItalyDepartment of Medicine, Surgery and Dentistry, Ospedale San Paolo, Medical Genetics, Università degli studi di Milano, Milan, ItalyDepartment of Animal Pathology, Hygiene and Veterinary Public Health, Università degli Studi di Milano and Fondazione Filarete, Milan, ItalyDepartment of Medicine, Surgery and Dentistry, Ospedale San Paolo, Medical Genetics, Università degli studi di Milano, Milan, ItalyDepartment of Experimental and Clinical Biomedical Sciences, Università dell'Insubria, Varese, ItalyDepartment of Medicine, Surgery and Dentistry, Pathology Unit, Ospedale San Paolo, Università degli studi di Milano, and Fondazione IRCCS Ca' Granda, Pathology Unit, Ospedale Maggiore Policlinico, Milan, ItalyUnit of Clinical Epileptology and Experimental Neurophysiology, Fondazione I.R.C.C.S. Istituto Neurologico “C. Besta”, Milan, ItalyNeural Stem Cell Biology Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, ItalyDepartment of Neurological Science, Fondazione IRCCS Ospedale Maggiore Policlinico, Università degli studi di Milano, and Istituto Clinico Humanitas, Milan, ItalyDepartment of Medicine, Surgery and Dentistry, Ospedale San Paolo, Medical Genetics, Università degli studi di Milano, Milan, ItalyBackground: MAP/microtubule affinity-regulating kinase 4 (MARK4) is a serine-threonine kinase expressed in two spliced isoforms, MARK4L and MARK4S, of which MARK4L is a candidate for a role in neoplastic transformation. Methods: We performed mutation analysis to identify sequence alterations possibly affecting MARK4 expression. We then investigated the MARK4L and MARK4S expression profile in 21 glioma cell lines and 36 tissues of different malignancy grades, glioblastoma-derived cancer stem cells (GBM CSCs) and mouse neural stem cells (NSCs) by real-time PCR, immunoblotting and immunohistochemistry. We also analyzed the sub-cellular localisation of MARK4 isoforms in glioma and normal cell lines by immunofluorescence. Results: Mutation analysis rules out sequence variations as the cause of the altered MARK4 expression in glioma. Expression profiling confirms that MARK4L is the predominant isoform, whereas MARK4S levels are significantly decreased in comparison and show an inverse correlation with tumour grade. A high MARK4L/MARK4S ratio also characterizes undifferentiated cells, such as GBM CSCs and NSCs. Accordingly, only MARK4L is expressed in brain neurogenic regions. Moreover, while both MARK4 isoforms are localised to the centrosome and midbody in glioma and normal cells, the L isoform exhibits an additional nucleolar localisation in tumour cells. Conclusions: The observed switch towards MARK4L suggests that the balance between the MARK4 isoforms is carefully guarded during neural differentiation but may be subverted in gliomagenesis. Moreover, the MARK4L nucleolar localisation in tumour cells features this MARK4 isoform as a nucleolus-associated tumour marker.http://dx.doi.org/10.3233/ACP-2011-0031 |
| spellingShingle | Ivana Magnani Chiara Novielli Laura Fontana Silvia Tabano Davide Rovina Ramona F. Moroni Dario Bauer Stefania Mazzoleni Elisa A. Colombo Gabriella Tedeschi Laura Monti Giovanni Porta Silvano Bosari Carolina Frassoni Rossella Galli Lorenzo Bello Lidia Larizza Differential Signature of the Centrosomal MARK4 Isoforms in Glioma Analytical Cellular Pathology |
| title | Differential Signature of the Centrosomal MARK4 Isoforms in Glioma |
| title_full | Differential Signature of the Centrosomal MARK4 Isoforms in Glioma |
| title_fullStr | Differential Signature of the Centrosomal MARK4 Isoforms in Glioma |
| title_full_unstemmed | Differential Signature of the Centrosomal MARK4 Isoforms in Glioma |
| title_short | Differential Signature of the Centrosomal MARK4 Isoforms in Glioma |
| title_sort | differential signature of the centrosomal mark4 isoforms in glioma |
| url | http://dx.doi.org/10.3233/ACP-2011-0031 |
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