Abstract
A role for the NF-kappaB family of transcription factors as tumor promoters is firmly established. However, other data suggest that NF-kappaB can also inhibit tumor growth. Moreover, NF-kappaB activity is modulated by tumor suppressors, such as p53 and ARF, whereby NF-kappaB subunits repress, rather than activate, the expression of tumor-promoting genes. This suggests a dual function of NF-kappaB during tumor progression - in the early stages, NF-kappaB inhibits tumor growth but, as further mutations lead to a loss of tumor suppressor expression, the oncogenic functions of NF-kappaB become unleashed, allowing it to actively contribute to tumorigenesis. Here, I discuss this hypothesis, its implications for NF-kappaB function, and how this might influence the use of NF-kappaB-based anticancer therapies.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Carcinogens / metabolism*
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Neoplastic / metabolism
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Cyclin-Dependent Kinase Inhibitor p16
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Gene Expression Regulation, Neoplastic / genetics
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Humans
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NF-kappa B / genetics*
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NF-kappa B / metabolism
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Neoplasms / genetics*
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Neoplasms / metabolism
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Oncogenes / genetics
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Tumor Suppressor Protein p14ARF / genetics
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Tumor Suppressor Protein p14ARF / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Proteins / genetics*
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Tumor Suppressor Proteins / metabolism
Substances
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Carcinogens
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Cdkn2a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p16
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NF-kappa B
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins