Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

IKKe coordinates invasion and metastasis

ABSTRACT: IKKe was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. In order to elucidate functional roles of IKKe, we used microarray analysis to identify genes changed upon IKKe shRNA knockdown and compared with genes affected in ovarian cancers IKKe was knockdowned by 2 different IKKe shRNAs in Ovcar5 in 6 replicates and candidate downstream targets were selected if changed by both shRNAs

ORGANISM(S): Homo sapiens

SUBMITTER: Marianne Kim

PROVIDER: E-GEOD-42320 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

IKK-ε coordinates invasion and metastasis of ovarian cancer.

Hsu Sarah S Kim Marianne M Hernandez Lidia L Grajales Valentina V Noonan Anne A Anver Miriam M Davidson Ben B Annunziata Christina M CM

Cancer research 20120831 21

Inhibitor of IκB kinases (IKK) are key regulators of NF-κB signaling. Three IKK isoforms-α, β, and ε-have been linked to oncogenesis, yet the precise components of NF-κB signaling in ovarian cancer have not yet been dissected. We surveyed 120 ovarian cancer specimens for IKK-ε expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumors (P = 0.03). Therefore, we hypothesized that IKK-ε drives ovarian cancer metastasis. IKK-ε was identified previously ...[more]

PMID: 22942254

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Project description:Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from epithelial ovarian cancer (EOC) patients, when compared to primary cultures derived from matched primary (prior to CT) tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic) stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis. To better understand the molecular mechanisms of RUNX2 gene action in ovarian cancer cells, we employed the Agilent Whole Human Genome microarrays, containing ~ 44,000 genes to identify global gene expression changes upon RUNX2 suppression in SKOV3 cells. We compared the gene expression of the previously selected clone shRNA- RUNX2-knockdown clone 3 (cl3) against the corresponding control clone. The microarray experiments were performed in duplicates, as two hybridizations were carried out for the RUNX2-suppressing cell clone against the corresponding control, using a fluorescent dye reversal (dye-swap) technique.

Dataset Information

IKKe coordinates invasion and metastasis

Publications

IKK-ε coordinates invasion and metastasis of ovarian cancer.

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