Suppression of invasion and peritoneal carcinomatosis of ovarian cancer cells by overexpression of AP-2alpha.
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.
Sumigama
Seiji
S
Department of Obstetrics and Gynecology, Nagoya Graduate University School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
Ito
Tomomi
T
Kajiyama
Hiroaki
H
Shibata
Kiyosumi
K
Tamakoshi
Koji
K
Kikkawa
Fumitaka
F
Williams
Trevor
T
Tainsky
Michael A
MA
Nomura
Seiji
S
Mizutani
Shigehiko
S
D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D004268:DNA-Binding Proteins; D020782:Matrix Metalloproteinases; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C493673:TFAP2A protein, human; C494918:AKT1 protein, human