Abstract
Cervical cancer is the second most common cancer in women. Inactivation of tumor suppressor genes underlies the transformation and progression of cervical cancer. Previously, we reported MAFIP can inhibit the growth of human cervical cancer HeLa cells. In this study, MAFIP was found to be downregulated in cervical intraepithelial neoplasia tissues. Induced expression of MAFIP in HeLa cells strongly inhibited tumor formation in nude mice, confirming its tumor suppressor activity in vivo. Overexpression of MAFIP inhibited activation of the NF-κB pathway, a commonly active pathway in cancer cells, by preventing the phosphorylation of IKK and IκBα, degradation of IκBα and the nuclear localization of p65. Induction of c-myc, an oncogene controlled by NF-κB, was severely impaired in the cells overexpressing MAFIP. In contrast, knockdown of MAFIP by siRNA activated the NF-κB pathway and promoted cell proliferation. These data suggest MAFIP functions as a tumor suppressor in cervical cancer in part by inhibiting activation of the NF-κB pathway.
© 2011 Japanese Cancer Association.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cytoskeletal Proteins
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Down-Regulation
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Female
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Gene Expression Regulation, Neoplastic
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HeLa Cells / metabolism
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Humans
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I-kappa B Kinase / metabolism
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I-kappa B Proteins / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Neoplasm Proteins / physiology*
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Phosphorylation
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Protein Processing, Post-Translational
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / physiology
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Signal Transduction
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / physiology*
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Uterine Cervical Dysplasia / genetics*
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Uterine Cervical Dysplasia / metabolism
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Uterine Cervical Dysplasia / pathology
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Uterine Cervical Neoplasms / genetics*
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Uterine Cervical Neoplasms / metabolism
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Uterine Cervical Neoplasms / pathology
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Xenograft Model Antitumor Assays
Substances
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Carrier Proteins
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Cytoskeletal Proteins
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I-kappa B Proteins
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MAFIP protein, human
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NF-kappa B
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NFKBIA protein, human
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Neoplasm Proteins
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Nfkbia protein, mouse
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Recombinant Fusion Proteins
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Tumor Suppressor Proteins
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NF-KappaB Inhibitor alpha
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I-kappa B Kinase