Fluvastatin-induced differential global gene expression in human malignant MCF-7 breast cancer cells
Ontology highlight
ABSTRACT: The current study analyzed the altered expression profiles of genes that are responsible for fluvastatin-induced breast cancer cell death in MCF-7 cells (ER+ve luminal breast cancer cells). Some of these altered gene expressions were further inter connceted to various pathways which may eventually be recognised as drug targets/ biomarkers in statin-sensitve breast cancer patients. To understand the differential gene expression profile in fluvastatin treated (24 h) malignant breast cancer cells with untreated malignant breast cancer cells.
Project description:The current study analyzed the altered expression profiles of genes that are responsible for fluvastatin-induced breast cancer cell death in MDA-MB-231 cells (ER-ve basal breast cancer cells). Some of these altered gene expressions were further inter connceted to various pathways which may eventually be recognised as drug targets/ biomarkers in statin-sensitve breast cancer patients. To understand the differential gene expression profile in fluvastatin treated (24 h) malignant breast cancer cells with untreated malignant breast cancer cells.
Project description:The current study analyzed the metadherin (MTDH)-mediated altered gene expression profiles in ER positive MCF-7 cells. Some of these altered gene expressions were further inter connected to various pathways which may eventually be recognized as drug targets or biomarkers in those breast cancers where MTDH plays a role in cancer progression/metastasis. To understand the global differential gene expression profile in MTDH-wild type and a newly identified MTDH-isoform knock down in malignant breast cancer cells. This data was compared to untreated breast cancer cells.
Project description:The current study analyzed the metadherin (MTDH)-mediated altered gene expression profiles in ER negative MDA-MB-231 cells. Some of these altered gene expressions were further inter connected to various pathways which may eventually be recognized as drug targets or biomarkers in those breast cancers where MTDH plays a role in cancer progression/metastasis. To understand the global differential gene expression profile in MTDH-wild type and a newly identified MTDH-isoform knock down in metastatic breast cancer cells. This data was compared to untreated breast cancer cells.
Project description:Purpose: We aimed to investigate in depth the regulation of microRNA expression by hypoxia in the breast cancer cell line MCF-7, establish the relationship between microRNA expression and HIF binding sites, pri-miRNA transcription and microRNA processing gene expression. Methods: microRNA sequencing data and gene expression microarray data were generated from MCF-7 cells submitted to an hypoxia timecourse (16h, 32h and 48h at 1% Oxygen). Data was integrated to 500 published high-stringency HIF binding sites identified in MCF-7 cells. Results: We identified 41 microRNAs significantly up- and 28 down- regulated, of which 38 mature and 20 star forms are reported in conjunction with hypoxia for the first time. HIF-1? and HIF-2? binding sites within 50kb distance of microRNA loci were found by integration of HIF ChIP-seq data, showing overall association between binding sites and up-regulation. Gene expression profiling analysis showed no full coordination between pri-miRNA and microRNA expression, pointing towards additional levels of regulation. Several transcripts playing a role in microRNA processing were found regulated by hypoxia, of which two were HIF dependent. Conclusions: The data support the hypothesis that microRNA expression under hypoxia is regulated at transcriptional and post-transcriptional level. HIF is involved at both levels, regulating the transcription of certain microRNAs and also the expression of key elements of the microRNA processing pathway. Gene expression profiles of MCF-7 exposed to hypoxia (1% Oxygen) for 16h (3 replicates), 32h (3 replicates) and 48h (3 replicates) and to normoxia (3 replicates) were generated using Illumina microarrays.
Project description:Background: Prostate cancer (PCa) cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome-wide mRNA expression changes in PCa cells in response to Runx2. Results: We engineered a C4-2B PCa sub-line called C4-2B/Rx2dox, in which doxycycline (Dox) treatment stimulates Runx2 expression from very low levels to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer-associated functions. They included secreted factors (CSF2, SDF-1), proteolytic enzymes (MMP9, CST7), cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A), intracellular signaling molecules (DUSP1, SPHK1, RASD1) and transcription factors (Sox9, SNAI2, SMAD3) functioning in epithelium to mesenchyme transition (EMT), tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal. Conclusions: The effects of Runx2 in C4-2B/Rx2dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is therefore an attractive target for the development of novel diagnostic, prognostic and therapeutic approaches to PCa management. Targeting Runx2 may prove more effective than focusing on its individual downstream genes and pathways. C4-2B/Rx2dox cells were subjected to microarray gene expression analysis after one and two days of treatment with either Dox or vehicle in biological quadruplicates (a total of 16 samples).
Project description:To identify microRNAs impacting estrogen receptor ERα expression in breast cancer, we have screened ER-positive breast cancer cells with a library of pre-miRs, and systematically monitored the ERα expression by protein lysate microarrays. There was a significant enrichment of the in silico predicted ERα targeting microRNAs among the hits. The most potent pre-miRs miR-18a/b, miR-193b, miR-206, and miR-302c, were confirmed to directly target ERα and to repress estrogen-responsive genes. The effect of miRNA overexpression on gene expression profile of MCF-7 cells was studied. Furthermore, miR-18a and miR-18b showed increased expression in ERα-negative as compared to ERα-positive clinical tumors. In summary, we present systematic and direct functional and correlative clinical evidence on microRNAs inhibiting ERα signaling in breast cancer. MCF-7 cells (300 000 per well on 6-well plates) were transfected with an siRNA for ERα or with Ambion pre-miR� constructs for miR-18a, miR-193b, miR-206, miR-302c, or pre-miR negative control #1 (scrambled pre-miR) at 20 nM, and incubated for 24h.
Project description:To characterize the molecular profile of the chorioamniotic membranes of preterm neonates with and without neurocognitive impairment at 18-24 months and (2) to determine if neonates who developed neurocognitive impairment can be identified at birth. Paired two-group design
Project description:ChIP-chip profiles of JIL-1, H3S10phK14ac and H4K16ac in Drosophila S2 cells JIL-1, H3S10phK14ac and H4K16ac ChIP in Drosophila S2 cells. 2-4 biological replicates per experiment. dye-swaps as indicated in sample description