Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional profiling of glucose deprivation resistant and glucose deprivation sensitive clones derived from IGROV-1 and SKOV3 ovarian cancer models and cultivated under either normal-glucose or low-glucose condition

ABSTRACT: This microarray experiment was designed to identify genes and pathways modulated in glucose deprivation resistant (GDR) and glucose deprivation sensitive (GDS) clones of ovarian cancer xenografts. Tumors were established in NOD/SCID mice by s.c. injection of human ovarian cancer cells (IGROV-1 and SKOV3). After sacrifice GDR and GDS clones were obtained from ex vivo cultures of tumors. Once isolated, GDR and GDS clones were cultivated in normal-glucose (0h) or low-glucose condition (6 h and 24 h). Two different time points were selected to investigate both early (6 h) and late (24 h) transcriptional effects of glucose deprivation in IGROV-1 and SKOV3-derived clones. Total RNA was extracted from samples and hybridized on Affymetrix GeneChip™ PrimeView™ Human Gene Expression Arrays. Based on assessment of RNA quality and on quality control analyses (including MAplots and boxplots), only one sample, corresponding to GDR condition at 6 h of glucose deprivation in SKOV3 model, was excluded because it was deemed not suitable for data analysis. In order to evaluate the effects of glucose deprivation in the two models, expression data of IGROV-1 and SKOV3-derived GDR and GDS clones were normalized and analyzed separately. Raw microarray data and pre-processed data matrices are available together with the applied protocols. Results of differential expression analysis are provided as supplementary tables of the associated publication.

ORGANISM(S): Homo sapiens

SUBMITTER: Angela Grassi

PROVIDER: E-MTAB-12150 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Epithelial ovarian cancer (EOC) accounts for 4% of all cancers in women and is the leading cause of death from gynecologic malignancies. It is well established that cancer invasion and metastasis still represent the major causes of the failure of cancer treatment. Previously, we identified the mannose receptor LY75 (DEC205/CD205) gene as notably hypomethylated in high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. LY75 has been identified as a putative antigen-uptake receptor, which is expressed abundantly on dendritic cells, which are specialist antigen presenting cells to T lymphocytes for the initiation of an immune response. The implication of LY75 in EOC tumorigenesis is currently unknown. Here we show that LY75 is strongly overexpressed in HG serous EOC tumors as compared to normal ovarian tissue. Importantly, shRNA-mediated LY75 knockout in the mesenchymal EOC cells (SKOV3) led to mesenchymal to epithelial transition (MET), associated with overexpression of epithelial markers E-cadherin and EPCAM and loss of expression of mesenchymal markers Fibronectin, N-cadherin Snail1 and Twist1. In addition, LY75 suppression significantly inhibited EOC cell migration and invasion in vitro. However, LY75 knockdown led to enhanced tumor cell dissemination and significantly increased lethality in vivo, in xenograft model of advanced peritoneal EOC. Thus, our findings indicate that LY75 could play an essential role in the mesenchymal-to-epithelial transition (MET) of EOC cells and support the hypothesis that, while epithelial-to-mesenchymal transition (EMT) enables the invasiveness of tumor cells, a MET-associated epithelial phenotype could be essential for their metastatic colonization. To better understand the molecular mechanisms of LY75 gene action in epithelial ovarian cancer (EOC), we employed the Agilent Whole Human Genome microarrays, containing ~ 44,000 genes to identify global gene expression changes upon LY75 suppression in SKOV3 EOC cells. We compared the gene expression of the previously selected shRNA-mediated LY75-knockdown clones sh-S3 and sh-S6 against the corresponding control (ctrl) clone. The microarray experiments were performed in duplicates, as two hybridizations were carried out for each of the LY75-suppressing cell clone against the corresponding control, using a fluorescent dye reversal (dye-swap) technique.

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

Transcriptional profiling of glucose deprivation resistant and glucose deprivation sensitive clones derived from IGROV-1 and SKOV3 ovarian cancer models and cultivated under either normal-glucose or low-glucose condition

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