Suppression of invasion and peritoneal carcinomatosis of ovarian cancer cells by overexpression of AP-2alpha |
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Authors: | Sumigama Seiji Ito Tomomi Kajiyama Hiroaki Shibata Kiyosumi Tamakoshi Koji Kikkawa Fumitaka Williams Trevor Tainsky Michael A Nomura Seiji Mizutani Shigehiko |
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Affiliation: | Department of Obstetrics and Gynecology, Nagoya Graduate University School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan. |
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Abstract: | A previous report demonstrated that AP-2alpha favors the survival of ovarian cancer patients by clinical findings. However, the functional roles of AP-2alpha in human ovarian cancers have not been determined. To clarify the roles, we overexpressed AP-2alpha in SKOV3 human ovarian cancer cells, which originally possess little AP-2alpha. AP-2alpha overexpression changed cell morphology from spindle to epithelioid type and suppressed cell proliferation and invasion, which would be partially correlated with decreased phosphorylation levels of the erbB2, Akt and ERK pathways, increased E-cadherin and reduced pro-matrix metalloproteinase-2 levels. Moreover, nude mice intraperitoneally injected with AP-2alpha-overexpressing cells survived longer than those with neo-transfected cells. The present data represent the first direct evidence that AP-2alpha plays a tumor suppressive role in ovarian cancer. |
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