MMSET Is Highly Expressed and Associated with Aggressiveness in Neuroblastoma
| Autor: | Ronald Simon, Maria Antonietta De Ioris, Lisa Leth Maroun, M Quarto, Henrik Daa Schrøder, Jens Vilstrup Johansen, Mette Rose Jørgensen, Eric Santoni-Rugiu, Kristian Helin, Guido Sauter, Zarah Glad Zimling, Bodil Laub Petersen, Julie Skotte, Michael Lees, Rossella Rota, Heidi Rye Hudlebusch, Catherine Rechnitzer |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Tissue microarray Cell growth Cellular differentiation Genes myc Cell Differentiation Chromosomal translocation Histone-Lysine N-Methyltransferase Biology Prognosis medicine.disease Molecular biology Neural stem cell Repressor Proteins Neuroblastoma Neural Stem Cells Oncology Cancer research medicine Humans Immunohistochemistry Progenitor cell Cell Proliferation |
| Zdroj: | Hudlebusch, H R, Skotte, J, Santoni-Rugiu, E, Zimling, Z G, Lees, M J, Simon, R, Sauter, G, Rota, R, De Ioris, M A, Quarto, M, Johansen, J V, Jørgensen, M, Rechnitzer, C M A, Maroun, L L, Schrøder, H, Petersen, B L & Helin, K 2011, ' MMSET is highly expressed and associated with aggressiveness in neuroblastoma ', Cancer Research, vol. 71, no. 12, pp. 4226-35 . https://doi.org/10.1158/0008-5472.CAN-10-3810 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | MMSET (WHSC1/NSD2) is a SET domain–containing histone lysine methyltransferase the expression of which is deregulated in a subgroup of multiple myelomas with the t(4;14)(p16;q32) translocation associated with poor prognosis. Recent studies have shown that MMSET mRNA levels are increased in other tumor types as well. We have carried out immunohistochemical staining of tissue microarrays and found that MMSET protein is frequently and highly expressed in neuroblastoma (MMSET positive in 75% of neuroblastomas, n = 164). The expression level of MMSET in neuroblastomas was significantly associated with poor survival, negative prognostic factors, and metastatic disease. Moreover, a subset of neuroblastomas for which pre- and postchemotherapy biopsies were available displayed a strong decrease in MMSET protein levels after chemotherapy. In agreement with neuroblastomas becoming more differentiated after treatment, we show that retinoic acid–induced differentiation of human neuroblastoma cells in vitro also leads to a strong decrease in MMSET levels. Furthermore, we show that the high levels of MMSET in normal neural progenitor cells are strongly downregulated during differentiation. Importantly, we show that MMSET is required for proliferation of neuroblastoma cells and brain-derived neural stem cells. Taken together, our results suggest that MMSET is implicated in neuroblastomagenesis possibly by supporting proliferation of progenitor cells and negatively regulating their differentiation. In this respect, MMSET might be a strong candidate therapeutic target in a subset of neuroblastomas with unfavorable prognosis. Cancer Res; 71(12); 4226–35. ©2011 AACR. |
| Databáze: | OpenAIRE |
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