The neural progenitor-restricted isoform of the MARK4 gene in 19q13.2 is upregulated in human gliomas and overexpressed in a subset of glioblastoma cell lines
| Autor: | John K. Cowell, Ivana Magnani, Gaetano Finocchiaro, Lidia Larizza, Simona Di Terlizzi, Ramona Frida Moroni, Tiziana Piepoli, Gaia Roversi, Alessandro Beghini, Anna Conti, Bianca Pollo |
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| Přispěvatelé: | Beghini, A, Magnani, I, Roversi, G, Piepoli, T, Di Terlizzi, S, Moroni, R, Pollo, B, Conti, A, Cowell, J, Finocchiaro, G, Larizza, L |
| Předmět: |
Gene isoform
Cancer Research Tumor suppressor gene Molecular Sequence Data human-malignant glioma human astrocytoma amplification Biology Protein Serine-Threonine Kinases epidermal-growth-factor factor receptor Glioma tumor-suppressor gene expression Gene duplication Genetics medicine Tumor Cells Cultured Humans Protein Isoforms Progenitor cell fragile site Molecular Biology In Situ Hybridization Fluorescence Sequence Deletion Wnt signaling pathway Cell Differentiation medicine.disease Neural stem cell Up-Regulation Cell culture Cancer research central-nervous-system Glioblastoma Chromosomes Human Pair 19 Neuroglia brain-tumor Cell Division |
| Zdroj: | Scopus-Elsevier Europe PubMed Central |
| Popis: | Alterations of 19q13 are frequently observed in glial neoplasms, suggesting that this region harbors at least one gene involved in gliomagenesis. Following our previous studies on structural 19q chromosome rearrangements in gliomas, we have undertaken a detailed FISH analysis of the breakpoints and identified a 19q13.2 intrachromosomal amplification of the MAP/microtubule affinity-regulating kinase 4 (MARK4) gene in three primary glioblastoma cell lines. Recent data suggest that this gene is involved in the Wnt-signating pathway. We observed that the expression of the alternatively spliced MARK4L isoform is upregulated in both fresh and cultured gliomas and overexpressed in all of the above three glioblastoma cell lines. Interestingly, we also found that MARK4L expression is restricted to undifferentiated neural progenitor cells or proliferating glial precursor cells, whereas its expression is downregulated during glial differentiation. Perturbation of expression using antisense oligonucleotides against MARK4 in glioblastoma cell tines, consistently induced a decreased proliferation of tumor cells. Taken together, these data show that MARK4, which is normally expressed in neural progenitors, is re-expressed in gliomas and may become a key target of intrachromosomal amplification upon 19q rearrangements. |
| Databáze: | OpenAIRE |
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