Early response of human ovarian and fallopian tube surface epithelial cells to norepinephrine
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA422427 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6376810_1.fastq.gz | Fastqsanger.gz | |||
| SRR6376810_2.fastq.gz | Fastqsanger.gz | |||
| SRR6376801_1.fastq.gz | Fastqsanger.gz | |||
| SRR6376801_2.fastq.gz | Fastqsanger.gz | |||
| SRR6376811_1.fastq.gz | Fastqsanger.gz |
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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.
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Project description:The transcriptomes of three immortalized ovarian surface epithelial cell lines (iOSE, PMID: 17266044) and primary OSE cells (Innoprot, Derio, Spain) and four immortalized fallopian tube secretory epithelial (iFTE) cell lines (PMID: 21502498, 22936217) were compared. RNA-sequencing was done from rRNA depleted total RNA (Ribo-Zero rRNA Removal Kit) to approx. 20 million 50 bp paired end reads per sample. A discriminative gene expression signature comprised of 211 genes was developed and used to classify isolated and EpCAM enriched primary ovarian cancer cells (PMID: 25991672). Impact of this signature on overall survival was assessed from several publicly available ovarian cancer gene expression data sets. Background: High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases. Comparative transcriptome analyses of isolated tumor cells from fresh HGSOC tissues and (immortalized) ovarian surface epithelial and fallopian tube secretory epithelial cell lines revealed a close relation between putative origin and tumor spread characteristic, i.e. miliary from tubes and non-miliary from ovaries.
2016-12-15 | E-MTAB-5240 | biostudies-arrayexpress
Project description:Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Ovarian cancer risk can be decreased by risk-reducing salpingo-oophorectomy (RRSO). Studies on RRSO material have altered the paradigm of serous ovarian cancer pathogenesis. The purpose of this study was to identify candidate genes possibly involved in pathogenesis of serous ovarian cancer by carrying out a microarray analysis of differentially expressed genes in BRCA1/2- mutation positive ovarian and fallopian tube epithelium derived from RRSO surgery. Freshly frozen ovarian and fallopian tube samples from nine BRCA1/2 mutation carriers scheduled for RRSO were prospectively collected in comparison with five mutation-negative control patients undergoing salpingo-oophorectomy for benign indications. Microarray analysis of genome-wide gene expression was performed on ovarian and fallopian tube samples from BRCA1/2 and control patients. The validation of microarray data was performed by quantitative real-time polymerase chain reaction (qRT-PCR) in selected cases of RRSO samples, and also high grade serous carcinoma samples collected from patients with BRCA phenotype. From 22,733 genes, 454 transcripts were identified that were differentially expressed in BRCA1/2 mutation carriers when statistically compared to controls pooling all ovarian and fallopian tube samples together. Of these, 299 genes were statistically significantly downregulated and 155 genes were upregulated. Differentially expressed genes in BRCA1/2 samples reported here might be involved in serous ovarian carcinogenesis and provide interesting targets for further studies. Both fallopian tube and ovarian samples were collected from each BRCA1/2 mutation carrier resulting in eighteen mutation positive adnexal samples. Both fallopian tube and ovarian control samples were collected from one control patient while either ovarian or fallopian tube sample was available from four control patients, respectively, resulting in 6 adnexal control samples. High quality RNA was available from nine BRCA1/2-mutation positive ovarian and eight BRCA1/2-mutation positive fallopian tube samples and from three control ovarian and three control fallopian tube samples.
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Project description:Comparison of gene expression profiling among high-grade ovarian epithelial cancer, ovarian epithelium and fallopian tube which might indicate the origin and carcinogenesis of ovarian cancer
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Project description:Fallopian tube epithelium is the tissue-of-origin of most high grade serous papillary ovarian carcinoma. This tumor has been exensively investigated and sequenced but expression profiling data of normal fallopian tube epithelial cells is still rare. This project compares the miRNA profiles of high grade serous papillary ovarian tumors (FFPE and fresh frozen) to that of normal unmatched epithelial cells from resected fallopian tubes.
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Project description:We analysed the extracellular matrix (ECM) landscape of fresh, healthy tissues from human fallopian tube (FT), fimbria (FB, the tissue of origin of serous tubal intraepithelial lesions) and ovarian tissue (OV). The aim was to identify differentially expressed matrix proteins between FB and FT or OV which may promote the neoplastic transformation of serous tubal intraepithelial lesions (STICs) into high-grade serous ovarian cancer, HGSOC, and metastasis from the FB to the OV.
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Project description:Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histologic analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal appearing p53-positive epithelium that are similar to “p53 signatures” in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these noninvasive precursor lesions, we also identified invasive adenocarcinoma in the ovary of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and WT C57BL/6. One of these genes, Top2a, which encodes topoisomerase II-alpha, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and specifically elevated in mouse STICs, but not in surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade, and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumorigenesis, as well as for developing novel approaches for the prevention, diagnosis, and therapy of this disease. Keywords: transgenic mouse model, ovarian cancer, fallopian tube, intraepithelial carcinoma 6 mouse fallopian tubes (FT) were analyzed with experimental repeats; 3 wildtype C57BL6 mice (FT) and 3 transgenic mogp-TAg (FT), with one set of each at 7, 8 and 9 weeks of age.
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Project description:The goal of this study was to identify transcriptional changes that occur in response to long-term norepinephrine (NE) treatment on normal immortalized fallopian tube cells (iFTSEC283). We treated isogenic cell lines (iFTSEC283 and iFTSEC283p53R175H) with 10μM NE or vehicle control (water) for 137 days with media change every two days followed by whole-transcriptome RNA seq. We identified 123 differentially expressed genes in 10μM NE vs mock-treated iFTSEC283. In iFTSEC283p53R175H cells, we identified 23 differentially expressed genes in response to chronic NE treatment.
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