Abstract
We have previously shown that forced expression of the transcription factor Scl in WEHI-3B D(+) cells prevents ATRA-induced cell differentiation. We now find that the overexpression of Rbtn2 also interferes with induction of differentiation by ATRA. Addition of LiCl to ATRA treatment restored the capacity of both Scl- and Rbtn2-expressing cells to respond to the retinoid in a synergistic manner. Similar results were obtained with Scl-transfected HL60 cells where its expression diminished responsiveness to ATRA. These findings suggest that if Scl and/or Rbtn2 are involved in the non-responsiveness of AML patients to ATRA-induced differentiation, addition of LiCl may reverse insensitivity.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic / pharmacology*
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Animals
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Antineoplastic Agents / pharmacology*
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Basic Helix-Loop-Helix Transcription Factors
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Blotting, Western
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Cell Differentiation / drug effects
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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Drug Synergism
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HL-60 Cells
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Humans
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LIM Domain Proteins
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Leukemia / metabolism*
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Lithium Chloride / pharmacology*
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Metalloproteins / biosynthesis
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Metalloproteins / genetics
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
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Transfection
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Tretinoin / pharmacology*
Substances
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic
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Antineoplastic Agents
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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LIM Domain Proteins
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LMO2 protein, human
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Metalloproteins
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Proto-Oncogene Proteins
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Transcription Factors
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TAL1 protein, human
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Tretinoin
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Lithium Chloride