Abstract
Myeloid cell leukemia sequence 1 (MCL1) is a potent antiapoptotic protein that plays a critical role in cell survival and drug resistance in various cancers. However, to the best of our knowledge, the role of MCL1 in mast cell tumors (MCTs) has not been investigated in dogs. Here, we detected increased MCL1 expression in MCT cell lines, regardless of the presence of a c-kit mutation. MCL1 expression increased when the cells were exposed to specific inhibitors of mitogen-activated protein kinase or Janus kinase-signaling pathways, thus protecting the cells from apoptosis, but not when KIT or phosphatidylinositol-3 kinase signaling cascades were inhibited. These results indicate that MCL1 expression may contribute to MCT survival and confer drug resistance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzamides / pharmacology
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Chromones / pharmacology
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Dog Diseases / metabolism*
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Dogs
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Electrophoresis, Polyacrylamide Gel / veterinary
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Flavonoids / pharmacology
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Gene Expression Regulation / drug effects*
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Gene Expression Regulation / physiology
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Imatinib Mesylate
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Janus Kinases / antagonists & inhibitors
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Mastocytoma / metabolism
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Mastocytoma / veterinary*
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Morpholines / pharmacology
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Myeloid Cell Leukemia Sequence 1 Protein / metabolism*
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Piperazines / pharmacology
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Pyrimidines / pharmacology
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Sirolimus / pharmacology
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Tyrphostins / pharmacology
Substances
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Benzamides
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Chromones
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Flavonoids
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Morpholines
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Myeloid Cell Leukemia Sequence 1 Protein
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Piperazines
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Pyrimidines
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Tyrphostins
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alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Imatinib Mesylate
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Janus Kinases
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Extracellular Signal-Regulated MAP Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Sirolimus