Activation of STAT3/5 signal pathways in complete mole and repression in choriocarcinoma cell lines.
OBJECTIVE
Because our previous study of microarray suggested that STAT5 and its downstream target, survivin, were up-regulated in complete mole (CM), we clarified the status of STAT-mediated signal transduction in CM and choriocarcinoma (CC).


METHODS
Proteins from 4 CM and normal villi and from 3 CC cell lines were subjected to Western blot (WB) analysis to evaluate STAT3 and 5 activation. After STAT and MEK inhibitor were added to these cells, the change in survivin expression was analyzed. Immunohistochemical staining was also done on CM and normal villi.


RESULTS
WB showed that phosphorylated STAT3 and 5, which are active forms of STAT protein, as well as survivin, were significantly up-regulated in CM. Immunohistochemistry showed positive signals of pSTATs in the cytotrophoblast and syncytiotrophoblast layer in CM but not in normal villi. In contrast, the pSTAT signal was hardly detected by WB in CC cells. However, a high level of survivin expression was maintained in CC by activation of the MEK signal pathway.


CONCLUSIONS
An activated STAT signal may contribute to hyperplastic cell growth of trophoblasts in CM. CC cells might be obtained independently of cytokine signals for tumor cell growth during the carcinogenic process.
Division of Molecular and Cell Therapeutics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Tsurumihara 4546, Beppu City, Oita 874-0838, Japan. hidekato@beppu.kyushu-u.ac.jp
Hidenori
H
Kato
Takafumi
T
Inoue
Kazuo
K
Asanoma
Takao
T
Matsuda
Yasuji
Y
Yoshikawa
Norio
N
Wake
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000235:genetics*; D002824:Chorionic Villi / Q000737:chemistry; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics*; D011247:Pregnancy; D050796:STAT3 Transcription Factor / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000235:genetics; D015398:Signal Transduction; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000235:genetics*
D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor