Abstract
This study investigates the dynamic regulation of human hematopoietic cell kinase (HCK) in acute promyelocytic leukemia (APL) and the underlying molecular mechanisms. First, the level of HCK in APL blasts was found lower than that in normal granulocytes and monocytes. Second, the HCK promoter was repressed by PML/RARα and this repression required PU.1. PU.1 was capable of transactivating the HCK promoter through a region encompassing three PU.1 motifs. Chromatin immunoprecipitation assays provided evidence that PU.1 and PML/RARα bound to the HCK promoter in vivo. Finally, we found an unequivocal increase of HCK expression upon treatment with all-trans retinoic acid.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Blotting, Western
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Cell Differentiation / drug effects
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Chromatin Immunoprecipitation
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Gene Expression Regulation, Neoplastic*
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Humans
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Leukemia, Promyelocytic, Acute / drug therapy
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Leukemia, Promyelocytic, Acute / genetics*
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Leukemia, Promyelocytic, Acute / metabolism
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Luciferases / metabolism
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Mutagenesis, Site-Directed
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Mutation / genetics
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-hck / genetics*
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Proto-Oncogene Proteins c-hck / metabolism
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Tretinoin / pharmacology
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins
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RNA, Messenger
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Trans-Activators
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promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
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proto-oncogene protein Spi-1
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Tretinoin
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Luciferases
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HCK protein, human
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Proto-Oncogene Proteins c-hck