Abstract
p18(Ink4c) functions as a dedicated inhibitor of cyclin-D-dependent kinases. Loss of Ink4c predisposes mice to tumor development and, in a dose-dependent manner, complements the tumor-promoting effects of various oncogenes. We have now addressed whether Ink4c loss impacts B-cell tumor development in the Emu-Myc transgenic mouse, a model of human Burkitt lymphoma. Loss of one or both alleles did not influence the onset of lymphoma in Emu-Myc transgenics, and did not appreciably affect Myc's proliferative or apoptotic responses in precancerous B cells. Nevertheless, Ink4c loss modulated the effects of Myc-induced transformation by decreasing the frequency of Arf loss, an ordinarily common event in Emu-Myc-induced lymphomas.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Cell Proliferation
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Cyclin-Dependent Kinase Inhibitor p16 / genetics
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Cyclin-Dependent Kinase Inhibitor p18 / genetics
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Cyclin-Dependent Kinase Inhibitor p18 / physiology*
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Disease Progression
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Gene Expression Regulation, Neoplastic
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Genes, Immunoglobulin Heavy Chain
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Lymphoma, B-Cell / genetics*
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Lymphoma, B-Cell / pathology
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Lymphoma, B-Cell / prevention & control*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / physiology
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / physiology*
Substances
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Cdkn2a protein, mouse
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Cdkn2c protein, mouse
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p18
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Myc protein, mouse
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins c-myc