Roesch, Alexander ; Fukunaga-Kalabis, Mizuho ; Schmidt, Elizabeth C. ; Zabierowski, Susan E. ; Brafford, Patricia A. ; Vultur, Adina ; Basu, Devraj ; Gimotty, Phyllis ; Vogt, Thomas ; Herlyn, Meenhard
Alternative Links zum Volltext:DOIVerlag
| Dokumentenart: | Artikel |
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| Titel eines Journals oder einer Zeitschrift: | Cell |
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| Verlag: | CELL PRESS |
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| Ort der Veröffentlichung: | CAMBRIDGE |
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| Band: | 141 |
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| Nummer des Zeitschriftenheftes oder des Kapitels: | 4 |
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| Seitenbereich: | S. 583-594 |
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| Datum: | 2010 |
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| Institutionen: | Medizin > Lehrstuhl für Dermatologie und Venerologie |
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| Identifikationsnummer: | | Wert | Typ |
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| 10.1016/j.cell.2010.04.020 | DOI |
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| Stichwörter / Keywords: | CANCER STEM-CELLS; TRANSCRIPTIONAL REPRESSION; METASTATIC MELANOMA; BREAST-CANCER; BINDING; PLU-1; IDENTIFICATION; PROGRESSION; EXPRESSION; LEUKEMIA; |
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| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin |
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| Status: | Veröffentlicht |
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| Begutachtet: | Ja, diese Version wurde begutachtet |
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| An der Universität Regensburg entstanden: | Ja |
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| Dokumenten-ID: | 66126 |
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Web of Science
Zusammenfassung
Melanomas are highly heterogeneous tumors, but the biological significance of their different subpopulations is not clear. Using the H3K4 demethylase JARID1B (KDM5B/PLU-1/RBP2-H1) as a biomarker, we have characterized a small subpopulation of slow-cycling melanoma cells that cycle with doubling times of >4 weeks within the rapidly proliferating main population. Isolated JARID1B-positive melanoma ...
Zusammenfassung
Melanomas are highly heterogeneous tumors, but the biological significance of their different subpopulations is not clear. Using the H3K4 demethylase JARID1B (KDM5B/PLU-1/RBP2-H1) as a biomarker, we have characterized a small subpopulation of slow-cycling melanoma cells that cycle with doubling times of >4 weeks within the rapidly proliferating main population. Isolated JARID1B-positive melanoma cells give rise to a highly proliferative progeny. Knockdown of JARID1B leads to an initial acceleration of tumor growth followed by exhaustion which suggests that the JARID1B-positive subpopulation is essential for continuous tumor growth. Expression of JARID1B is dynamically regulated and does not follow a hierarchical cancer stem cell model because JARID1B-negative cells can become positive and even single melanoma cells irrespective of selection are tumorigenic. These results suggest a new understanding of melanoma heterogeneity with tumor maintenance as a dynamic process mediated by a temporarily distinct subpopulation.
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