期刊
CANCER SCIENCE
卷 102, 期 11, 页码 2043-2050出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1349-7006.2011.02061.x
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资金
- National Key Basic Research and Development Plan of China (973 program) [2009CB825601]
- National Nature Science Foundation of China [NSFC 30771145, 30671175]
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-kappa B pathway, a commonly active pathway in cancer cells, by preventing the phosphorylation of IKK and I kappa B alpha, degradation of I kappa B alpha and the nuclear localization of p65. Induction of c-myc, an oncogene controlled by NF-kappa B, was severely impaired in the cells overexpressing MAFIP. In contrast, knockdown of MAFIP by siRNA activated the NF-kappa B 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-kappa B pathway. (Cancer Sci 2011; 102: 2043-2050)
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