ABSTRACT: Paired platinum-sensitive & platinum-resistant cell lines PEO1 and PEO4 (respectively) were derived from the same patient. Cell line cultures were profiled with the HT-HGU133a GeneChip to investigate chemotherapy resistance related expression of genes marked with different histone modifications in a primary ovarian tumour (clinical data for the primary ovarian tumour is available as Series supplementary file). 4 replicates of each of the PEO1 and PEO4 cell line were profiled using the HT-HGU133a GeneChip
Project description:Paired platinum-sensitive & platinum-resistant cell lines PEO1 and PEO4 (respectively) were derived from the same patient. Cell line cultures were profiled with the HT-HGU133a GeneChip to investigate chemotherapy resistance related expression of genes marked with different histone modifications in a primary ovarian tumour (clinical data for the primary ovarian tumour is available as Series supplementary file).
Project description:This SuperSeries is composed of the following subset Series: GSE41498: Profiling of ovarian tumour and benign lesions GSE41499: Expression profiling of ovarian cancer cell lines Refer to individual Series
Project description:Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER)-positive breast cancers resistant to the antiestrogen, tamoxifen. In this study, biomarkers co-ordinately up-regulated by NFKB and AP-1 with prognositic significance are identified in a largely TAM-treated set of ER+ node negative breast cancers. The prognostic value with respect to age is also investigated. Experiment Overall Design: 54 ER+ node negative breast tumors with known clinical outcome were analyzed. Genes co-ordinately regulated by NFKB and AP1from literature are identified from a significant gene set obtained through a minimum variation filter. Biomarker expression is used to dichotomize samples into high vs. low expressors to determine prognostic value
Project description:To investigate the biological basis between aging and sporadic breast cancer incidence and prognosis, RNA samples from matched ER+ invasive breast cancers diagnosed in either young (â?¤45) or old (â?¥70) women were analyzed by expression microarrays Experiment Overall Design: ER+ breast cancers collected from either young or old women, well matched for other clinical parameters were analyzed using expression microarrays. Age associated tumor subtypes and enrichment of pre-defined gene signatures were identified. Age associated differential expression and an age signature (gene-based classifier) was assessed
Project description:To investigate the oxidant sensitivity of E/ER regulated gene expression, E/ER regulated genes are identified using E deprivation or; ER-alpha siRNA knockdown; and oxidative stress responsive is determined by 8hr exposure to diamide, hydrogen peroxide and menadione Experiment Overall Design: MCF7 cells were treated under various conditions to identifiy oxidative stress responsive E/ER regulated genes. Association of these genes with respect to tumor phenotypes are assessed
Project description:G-quadruplexes are secondary DNA structures which have been shown to have an impact on gene transcription via a variety of mechanisms, In this study we generate RNA-seq data of wildtype chemotherpay sensitive (PEO1 A) and chemostherapy resistant (PEO4 A) ovarian cancer cells to intersect with G-quadruplex mapping data to assess how transcription is impacted by G-quadruplex formation. In another variation of the PEO1/4 cell line, in which the PEO1 B cell line has a reversion mutation to reinstate BRCA2, we used the G-quadruplex stabilising molecule pyridostatin (PDS) to treat PEO1 B and its counterpart PEO4 B for either 0, 2 or 6 hours to see how stabilising G-quadruplexes effects gene expression in a temporal manner.
Project description:Enhancers are regulatory elements of the genome involved in transcriptional regulation and reprogramming. Similarly, we propose that secondary DNA structures termed G-quadruplexes could also be impacting transcription in an enhancer based way via long-range interactions to bring together regulatory elements of the genome. In this study, we map G-quadruplex structures and h3k27ac enhancer marks in a paired ovarian cancer cell line; PEO1 and PEO4. We endeavour to use these findings to help link the transcriptional function of G-quadruplexes with enchancer in chemotherapy sensitive (PEO1) and chemotherapy resistant (PEO4) ovarian cancer cells.
Project description:Background: Tumor heterogeneity is one of the key factors leading to chemo-resistance relapse. It remains unknown how resistant cancer cells influence sensitive cells during cohabitation and growth within a heterogenous tumors. The goal of our study was to identify driving factors that mediate the interactions between resistant and sensitive cancer cells and to determine the effects of cohabitation on both phenotypes. Methods: We used isogenic ovarian cancer cell (OC) lines pairs, sensitive and resistant to platinum: OVCAR5 vs. OVCAR5 CisR and PEO1 vs. PEO4, respectively, to perform long term direct culture and to study the phenotypical changes of the interaction of these cells. Results: Long term direct co-culture of sensitive and resistant OC cells promoted proliferation (p < 0.001) of sensitive cells and increased the proportion of cells in the G1 and S cell cycle phase in both PEO1 and OVCAR5 cells. Direct co-culture led to a decrease in the IC50 to platinum in the cisplatin-sensitive cells (5.92 µM to 2.79 µM for PEO1, and from 2.05 µM to 1.51 µM for OVCAR5). RNAseq analysis of co-cultured cells showed enrichment of Cell Cycle Control, Cyclins and Cell Cycle Regulation pathways. The transcription factor E2F1 was predicted as the main effector responsible for the transcriptomic changes in sensitive cells. Western blot and qRT-PCR confirmed upregulation of E2F1 in co-cultured vs monoculture. Furthermore, an E2F1 inhibitor reverted the increase in proliferation rate induced by co-culture to baseline levels. Conclusions: Our data suggest that long term cohabitation of platinum-sensitive and -resistant cancer cells drive sensitive cells to a higher proliferative state, more responsive to platinum. Our results reveal an unexpected effect caused by direct interactions between cancer cells with different proliferative rates and levels of platinum resistance, modelling competition between cells in heterogeneous tumors.
Project description:G-quadruplex ChIP-seq has been performed to establish genomic maps of G-quadruplex structures in chemotherapy sensitive (PEO1) and chemotherapy resistant (PEO4) ovarian cancer cell lines to uncover how the changes in G-quadruplex landscape may contribute to the development of chemotherapy resistance for the first time.