Identification of circadian-related gene expression profiles in entrained breast cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Sean-Patrick Scott
PROVIDER: E-GEOD-76370 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Cancer cells have broken circadian clocks as compared to their normal tissue counterparts. Moreover, it has been shown in breast cancer that disruption of common circadian oscillations are associated to worse prognosis. Numerous studies focused at conical circadian genes in breast cancer cell lines have suggested that there are no mRNA circadian-like oscillations. Nevertheless, cancer cell lines have not been extensively characterized and it is unknown to what extent the circadian oscillations are disrupted. We have chosen representative breast cancer cell lines (MCF-10A, MCF-7, ZR-75-30, MDA-MB-231, and HCC-1954) in order to determine the degree which the circadian clock is damaged. We used serum shock to synchronize the circadian clocks in culture. Our aim was to observe the time course of gene expression using cDNA microarrays in the noncancerous MCF-10A and the cancerous MCF-7 cells and characterize specific genes in other cell lines. We used a cosine function to select highly correlated profiles. Some of the identified genes were validated by qPCR and further evaluated in the other breast cancer cell lines. Interestingly, we observed that breast cancer and noncancerous cultured cells are able to generate specific circadian expression profiles in response to the serum shock. The rhythmic genes suggested via microarray and measured in each particular subtype suggest that each breast cancer cell type respond differently to the circadian synchronization. Future results could identify circadian-like genes that are altered in breast cancer and noncancerous cells which can be used to propose novel treatments. Breast cell lines are potential models for in vitro studies of circadian clocks and clock-controlled pathways. There are 8 total samples representing 0 to 28 hours in 4 hour intervals in MFC-10A breast noncancerous epitheleal cell line.
2016-04-01 | E-GEOD-76369 | biostudies-arrayexpress
Project description:Cancer cells have broken circadian clocks as compared to their normal tissue counterparts. Moreover, it has been shown in breast cancer that disruption of common circadian oscillations are associated to worse prognosis. Numerous studies focused at conical circadian genes in breast cancer cell lines have suggested that there are no mRNA circadian-like oscillations. Nevertheless, cancer cell lines have not been extensively characterized and it is unknown to what extent the circadian oscillations are disrupted. We have chosen representative breast cancer cell lines (MCF-10A, MCF-7, ZR-75-30, MDA-MB-231, and HCC-1954) in order to determine the degree which the circadian clock is damaged. We used serum shock to synchronize the circadian clocks in culture. Our aim was to observe the time course of gene expression using cDNA microarrays in the noncancerous MCF-10A and the cancerous MCF-7 cells and characterize specific genes in other cell lines. We used a cosine function to select highly correlated profiles. Some of the identified genes were validated by qPCR and further evaluated in the other breast cancer cell lines. Interestingly, we observed that breast cancer and noncancerous cultured cells are able to generate specific circadian expression profiles in response to the serum shock. The rhythmic genes suggested via microarray and measured in each particular subtype suggest that each breast cancer cell type respond differently to the circadian synchronization. Future results could identify circadian-like genes that are altered in breast cancer and noncancerous cells which can be used to propose novel treatments. Breast cell lines are potential models for in vitro studies of circadian clocks and clock-controlled pathways. There are 8 total samples representing 0 to 28 hours in 4 hour intervals in MFC-7 breast cancer epitheleal cell line.
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Project description:Methylated DNA binding protein 2 (MBD2) has been shown to bind specific methylated promoters and suppress transcription. Here we systematically investigate MBD2 suppression by overexpressing MBD2 in MCF-10A cells and generating gene expression profiles of overexpressing cells and normal MCF-10A cells. MCF-10A cells were infected with MBD2 lentivirus in order to increase MBD2 expression. Total RNA was extracted from both infected and non-infected cells and hybridized to Affymetrix gene expression microarrays. Three technical replicates were hybridized for infected and non-infected cells.
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Project description:Analysis of MCF-7 cells treated for 4h with Ethanol, Estradiol (E2), Dexamethasone (Dex), or Estradiol + Dexamethasone (E2 + Dex) In estrogen receptor (ER)-negative breast cancer (BC), high tumor glucocorticoid receptor (GR) expression has been associated with a relatively poor outcome. In contrast, using a meta-analysis of several genomic datasets, here we find that tumor GR mRNA expression is associated with improved ER+ relapse-free survival (RFS) (independently of progesterone receptor (PR) expression). To understand the mechanism by which GR expression is associated with a better ER+ BC outcome, the global effect of GR-mediated transcriptional activation in ER+ BC cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in ER+/GR+ MCF-7 cells revealed that upon co-activation of GR and ER, GR chromatin association became enriched at proximal promoter regions. Furthermore, following ER activation, increased association of GR was observed at ER, FOXO, and AP1 response elements. In addition, it was determined that ER associated with GR response elements, suggesting that ER and GR interact in a complex. Co-activation of GR and ER resulted in increased expression (relative to ER activation alone) of transcripts that encode proteins promoting cellular differentiation (e.g. KDM4B, VDR) and inhibiting Wnt-signaling (IGFBP4). Finally, expression of these individual pro-differentiation genes was associated with significantly improved RFS in ER+ BC patients. Together, these data demonstrate that the co-expression and subsequent activity of tumor cell GR and ER contribute to the less aggressive natural history of early-stage BC by coordinating the altered expression of genes favoring differentiation. Four treatment samples (Vehicle V, Dex D, E2, or Dex+E2). Three biological replicate experiments per sample. Vehicle sample is Ethanol control.
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Project description:Expression profiles of MCF-7 cells treated with Fulvestrant (ICI 182,780) and vehicle Experiment Overall Design: MCF7 cells were grown in DMEM supplemented with 5% FCS (Hyclone, "Defined" grade). Growth medium was changed immediately before addition of 100 nM of ICI 182,780 or vehicle alone (0.1% ethanol) and cells incubated for 48h before they were harvested for profiling. Note that MCF7 cells show no signs of cell damage at this time point.
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Project description:Expression of estrogen receptor (ESR1) determines whether a breast cancer patient receives endocrine therapy as part of their adjuvant care, but does not guarantee patient response. However, the molecular factors that define endocrine response in ESR1-positive breast cancer patients remain poorly understood. Here, we characterize the DNA methylome of endocrine sensitivity and demonstrate the potential impact of differential DNA methylation on endocrine response in breast cancer. We show that DNA hypermethylation occurs predominantly at estrogen-responsive enhancers and is associated with reduced ESR1 binding and decreased gene expression of key regulators of ESR1-activity; thus providing a novel mechanism by which endocrine response is abated in ESR1-positive breast cancers. Conversely, we delineate that ESR1-responsive enhancer hypomethylation is critical in transition from normal mammary epithelial cells to endocrine responsive ESR1-positive cancer. Cumulatively these novel insights highlight the potential of ESR1-responsive enhancer methylation to both predict ESR1-positive disease and stratify ESR1-positive breast cancer patients as responders to endocrine therapy. Methylation profiling with Illumina's HumanMethylation450K array was performed on ESR1-positive hormone sensitive MCF7 cells, and three different well characterised endocrine resistant MCF7-derived cell lines; tamoxifen-resistant (TAMR), fulvestrant-resistant (FASR) and estrogen deprivation resistant (MCF7X) cells. For each cell line two biological replicates were profiled bringing the number of samples to eight.
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Project description:To evaluate the function of ALK in breast cancer, we enforcing expressed full length wild type ALK in the parental MCF-7 breast cancer cell line that we have established in previous studies have a very low invasive capacity, do not form tumor emboli nor do they invade into the dermal lymphatics when grown as xenografts. Whole unbiased transcriptome analysis were performed using ALK over-expressed MCF-7 clones and control clones. Pathway mapping revealed that the presence of ALK induced up and down regulation changes of series of genes within several canonical signal pathway.
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