Title
The RUNX1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasion The RUNX1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasion
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
,
Subject
Biology
Human medicine
Source (journal)
Cell cycle. - Place of publication unknown
Volume/pages
12(2013) :6 , p. 972-986
ISSN
1538-4101
ISI
000316186800021
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Previously, we have identified the RUNX1 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from epithelial ovarian cancer (EO C) patients, when compared with primary cultures derived from matched primary (prior to CT) tumors. Here we show that RUNX1 displays a trend of hypomethylation, although not significant, in omental metastases compared with primary EO C tumors. Surprisingly, RUNX1 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. The RUNX1 expression levels were almost identical in primary tumors and omental metastases, suggesting that RUNX1 hypomethylation might have a limited impact on its overexpression in advanced (metastatic) stage of the disease. Knockdown of the RUNX1 expression in EO C cells led to sharp decrease of cell proliferation and induced G(1) cell cycle arrest. Moreover, RUNX1 suppression significantly inhibited EO C cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EO C tumor invasion and metastasis, were found to be down-regulated upon RUNX1 suppression, while a number of pro-apoptotic genes and some EO C tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX1 gene in EO C progression and suggest that RUNX1 might be a novel EO C therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX1 and other members of the RUNX gene family in ovarian tumorigenesis.
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