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Expression data from mouse SEOC tumors

ABSTRACT: We have developed mouse models for serous epithelial ovarian cancer (SEOC) based on conditional inactivation of p53 and Rb tumor suppression (RB-TS) in combination with or without Brca1/2 following injection of adenovirus expressing Cre recombinase into the ovarian bursa. These models develop metastatic (Stage IV) disease with key histopathological features resembling human SEOC.To determine whether these mouse tumors resemble human SEOC at the molecular level, we conducted global gene expression analysis on 27 ovarian carcinomas and 3 pooled normal ovarian surface epithelium samples (single epithelial layer isolated from ovarian surface by laser capture).

ORGANISM(S): Mus musculus

PROVIDER: GSE46169 | GEO | 2013/04/19

SECONDARY ACCESSION(S): PRJNA197488

REPOSITORIES: GEO

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Expression data from mouse SEOC tumors

Project description:We have developed mouse models for serous epithelial ovarian cancer (SEOC) based on conditional inactivation of p53 and Rb tumor suppression (RB-TS) in combination with or without Brca1/2 following injection of adenovirus expressing Cre recombinase into the ovarian bursa. These models develop metastatic (Stage IV) disease with key histopathological features resembling human SEOC.To determine whether these mouse tumors resemble human SEOC at the molecular level, we conducted global gene expression analysis on 27 ovarian carcinomas and 3 pooled normal ovarian surface epithelium samples (single epithelial layer isolated from ovarian surface by laser capture). RNA was isolated from flash frozen ovarian tumors or from ovarian surface epithelial cells microdissected from frozen sections using PixCell IIe laser capture microdissection instrument.

2013-04-19 | E-GEOD-46169 | biostudies-arrayexpress

Genome-wide analysis of gene expression of mouse ovarian cancer cell lines generated in vivo and in vitro

2016-06-30 | GSE69544 | GEO

Expression analysis of murine primary and derived orthotopic SEOC tumors

Project description:We previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53, Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. We have adapted these GEM models to orthotopic allografts that uniformly develop tumors with short latency in immunocompetent recipients and are ideally suited for routine preclinical studies. To monitor passaged tumors at the molecular level, we analyzed transcriptional profiles of a set of primary SEOC and matching derived passaged tumors. We have merged this dataset with previously published ( doi: 10.1158/0008-5472.CAN-11-3834; PMID 22617326) dataset of murine primary ovarian tumors from our GEM models (GSE46169) and merged and compared them to expression profiles of human dataset published previously (doi: 10.1038/nature10166). The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value. We previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53, Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. Here, we describe an adaptation of these GEM models to orthotopic allografts that uniformly develop tumors with short latency and are ideally suited for routine preclinical studies. RNA was isolated from flash frozen ovarian tumors using Trizol and Qiagen RNeasy columns

2013-10-30 | E-GEOD-51927 | biostudies-arrayexpress

Early response of human ovarian and fallopian tube surface epithelial cells to norepinephrine

Project description:The purpose of this study is to understand the effects of adrenergic signaling on the transcriptome of cell line models postulated to be the cells of origin of epithelial ovarian cancers using RNA-Seq. Here we explored the effects of the stress-related hormone, norepinephrine, on normal human ovarian and fallopian tube surface epithelial cellss. We investigated the early transcriptional response to norepinephrine in normal immortalized ovarian surface epithelial cells and fallopian tube secretory cells. RNA-Seq data of treated and untreated cells were analyzed to identify genes with differential expression.

2018-05-25 | GSE108084 | GEO

Ovarian Cancer gene expression profiling identifies the surface of the ovary as a stem cell niche

Project description:In contrast to epithelial derived carcinomas that arise in most human organs, ovarian surface epithelial cells become more rather than less differentiated as the malignancy progresses. To test the hypothesis that ovarian surface epithelial cells retain properties of relatively uncommitted pluripotent cells until undergoing neoplastic transformation, we conducted gene expression profiling analysis (Affymetrix, U133 Plus 2.0) of 12 ovarian surface epithelial cells and 12 laser capture microdissected serous papillary ovarian cances. We find that over 2000 genes are significantly differentially expressed between the surface epithelial and cancer samples. Network analysis implicates key signaling pathways and pathway interactions in ovarian cancer development. Genes previously associated with adult stem cell maintenance are expressed in ovarian surface epithelial cells and significantly down-regulated in ovarian cancer cells. Our results indicate that the surface of the ovary is an adult stem cell niche and that deregulation of genes involved in maintaining the quiescence of ovarian surface epithelial cells is instrumental in the initiation and development of ovarian cancer.

2009-12-31 | GSE14407 | GEO

A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies

Project description:This is a two-part Phase 1/2 dose escalation and dose expansion study of an Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus), ONCOS-102, in combination with anti-programmed death ligand-1 (PD-L1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior standard chemotherapy and have histologically confirmed epithelial ovarian cancer or metastatic colorectal cancer.

| 2229839 | ecrin-mdr-crc

Genome-wide analysis of gene expression of mouse ovarian cancer cell lines generated in vivo and in vitro

Project description:Mouse ovarian cancer cells lines were generated from primary tumor tissues, metastatic tumor tissues and in vitro cultured ovarian bursa cells. Gene transcripts from the whole genome were tested using WG6 microarray to compare gene expression level of cells lines with and without Epithelial to Mesenchymal Transition(EMT). Total RNAs were isolated from different cell lines with two time points for each cell line and compare the differentially expressed genes in cell lines with different biological characteristics.

2016-06-30 | E-GEOD-69544 | biostudies-arrayexpress

Expression analysis of murine primary and derived orthotopic SEOC tumors

2013-10-30 | GSE51927 | GEO

Both Fallopian Tube and Ovarian Surface Epithelium Can Act as Cell-of-Origin for High Grade Serous Ovarian Carcinoma

Project description:The cell-of-origin of high grade serous ovarian carcinoma (HGSOC) remains controversial, with fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) both considered candidates. Here, by using genetically engineered mouse models and organoids, we assessed the tumor-forming properties of FTE and OSE harboring the same oncogenic abnormalities. Combined RB family inactivation and Tp53 mutation in Pax8+ FTE caused Serous Tubal Intraepithelial Carcinoma (STIC), which metastasized rapidly to the ovarian surface. These events were recapitulated by orthotopic injection of mutant FTE organoids. Engineering the same genetic lesions into Lgr5+ OSE or OSE-derived organoids also caused metastatic HGSOC, although with longer latency and lower penetrance. FTE- and OSE-derived tumors had distinct transcriptomes, and comparative transcriptomics and genomics suggest that human HGSOC arises from both cell types. Finally, FTE- and OSE-derived organoids exhibited differential chemosensitivity. Our results comport with a dualistic origin for HGSOC and suggest that the cell-of-origin might influence therapeutic response.

2019-10-21 | GSE125016 | GEO

TGFb/Smad4 targets promter in IOSE cells

Project description:Unlike ovarian cancer, normal ovarian epithelium response to TGFb1 induced growth inhibition. This study tried to idenify promoters that showed Smad4 binding after additionof TGFb1 in immortalized ovarian surface epithelial cells (IOSE) which is derived from normal ovarian epithelial cells Keywords: ChIP-chip

2007-01-13 | GSE6727 | GEO

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