Abstract
The dysregulated ERK and RB pathways often coexist in melanoma cells. The K-type human endogenous retrovirus (HERV-K) is implicated in melanomagenesis. Some of the phenotypes that are modified by HERV-K (e.g., changes in cell shape, melanin production, and anchorage-dependent growth) overlap with those that are regulated by ERK and RB pathways. As ERK signaling can regulate retroviruses, we hypothesized that HERV-K expression is controlled by ERK-RB pathways. We found that the levels of HERV-K GAG and EVE correlated with the activation of ERK and loss of p16INK4A and that inhibition of MEK or CDK4, especially in combination, reduced HERV-K EVE in melanoma cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Line, Tumor
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Cyclin-Dependent Kinase 4 / metabolism*
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Gene Expression
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Humans
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Immunohistochemistry
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MAP Kinase Kinase Kinases / metabolism*
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Melanoma / genetics
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Melanoma / metabolism*
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Signal Transduction / physiology
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Viral Proteins / biosynthesis*
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Viral Proteins / genetics
Substances
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Cyclin-Dependent Kinase Inhibitor p16
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HERV-K cORF protein, Human endogenous retrovirus K
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Viral Proteins
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Cyclin-Dependent Kinase 4
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Extracellular Signal-Regulated MAP Kinases
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MAP Kinase Kinase Kinases