Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mediator of DNA damage checkpoint 1 (MDC1) is a novel estrogen receptor co-regulator in invasive lobular carcinoma of the breast

ABSTRACT: Mediator of DNA damage checkpoint 1 (MDC1) is a novel estrogen receptor co-regulator in invasive lobular carcinoma of the breast

PROVIDER: PRJNA719219 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR14132700_1.fastq.gz	Fastqsanger.gz
	SRR14132700_2.fastq.gz	Fastqsanger.gz
	SRR14132701_1.fastq.gz	Fastqsanger.gz
	SRR14132701_2.fastq.gz	Fastqsanger.gz
	SRR14132702_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 90

Similar Datasets

Mediator of DNA damage checkpoint 1 (MDC1) is a novel estrogen receptor co-regulator in invasive lobular carcinoma of the breast

Project description:We identified MDC1 as a putative novel transcriptional co-regulator of estrogen receptor alpha (ER) in models of invasive lobular carcinoma. In this study, our goal was to define the contribution of MDC1 to regulation of the ER transcriptome in ILC cell lines versus invasive ductal carcinoma cells.

2021-05-13 | GSE171364 | GEO

Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Coregulator in Invasive Lobular Carcinoma of the Breast.

Project description:Invasive lobular carcinoma (ILC) is the most common special histologic subtype of breast cancer, and nearly all ILC tumors express estrogen receptor alpha (ER). However, clinical and laboratory data suggest ILC are strongly estrogen-driven but not equally antiestrogen-sensitive. We hypothesized ILC-specific ER coregulators mediate ER functions and antiestrogen resistance in ILC, and profiled ER-associated proteins by mass spectrometry. Three ER+ ILC cell lines (MDA MB 134VI, SUM44PE, and BCK4) were compared with ER+ invasive ductal carcinoma (IDC) line data, and we examined whether siRNA of identified proteins suppressed ER-driven proliferation in ILC cells. This identified mediator of DNA damage checkpoint 1 (MDC1), a tumor suppressor in DNA damage response (DDR), as a novel ER coregulator in ILC. We confirmed ER:MDC1 interaction was specific to ILC versus IDC cells, and found MDC1 knockdown suppressed ILC cell proliferation and tamoxifen resistance. Using RNA-sequencing, we found in ILC cells MDC1 knockdown broadly dysregulates the ER transcriptome, with ER:MDC1 target genes enriched for promoter hormone response elements. Importantly, our data are inconsistent with MDC1 tumor suppressor functions in DDR, but suggest a novel oncogenic role for MDC1 as an ER coregulator. Supporting this, in breast tumor tissue microarrays, MDC1 protein was frequently low or absent in IDC, but MDC1 loss was rare in ER+ ILC. ER:MDC1 interaction and MDC1 coregulator functions may underlie ER function in ILC and serve as targets to overcome antiestrogen resistance in ILC. IMPLICATIONS: MDC1 has novel ER coregulator activity in ILC, which may underlie ILC-specific ER functions, estrogen response, and antiestrogen resistance.

| S-EPMC8349796 | biostudies-literature

MDC1 maintains active elongation complexes of RNA polymerase II

Project description:The role of MDC1 in the DNA damage response has been extensively studied, however, its impact on other cellular processes is not well understood. Here, we describe a role for MDC1 in transcription by regulating the activity of the RNAPolymerase II (RNAPII). Depletion of MDC1 caused a genome-wide reduction in the abundance of actively engaged RNAPII elongation complexes throughout the gene body of protein coding genes under unperturbed conditions. Decreased engaged RNAPII subsequently alters the assembly of the spliceosome complex on chromatin, leading to defects in pre-mRNA splicing. Mechanistically, the S/TQ domain of MDC1 modulates RNAPII-mediated transcription. Upon genotoxic stress, MDC1 promotes the abundance of engaged RNAPII complexes at DNA breaks, thereby stimulating nascent transcription at the damaged sites. Of clinical relevance, cancer cells lacking MDC1 display hypersensitivity to RNAPII inhibitors. Overall, we unveil a previously uncharacterized role of MDC1 in RNAPII-mediated transcription with potential implications for cancer treatment.

2022-11-24 | GSE215990 | GEO

Analysis of microdissected invasive lobular and ductal breast carcinomas in relation to normal ductal and lobular cells

2007-03-16 | GSE5764 | GEO

Cdh1 and Pik3ca mutations cooperate to induce Immune-Related Invasive Lobular Carcinoma of the Breast

Project description:CDH1 and PIK3CA are the two most frequently mutated genes in Invasive Lobular Carcinoma (ILC) of the breast. Transcription profiling has identified molecular subtypes for ILC, one of which - Immune-Related (IR) - is associated with gene expression linked to lymphocyte and macrophage infiltration. Here we report that homozygous deletion of Cdh1 together with mutational activation of Pik3ca in mammary epithelium of genetically modified mice leads to rapid formation of IR-ILC-like tumors with immune cell infiltration, as well as gene expression signatures linked to TRegulatory (Treg) cell signaling and immune checkpoint inhibitor pathway activation. Interestingly, these tumors show enhanced Oct4-, Hif1á-, YAP-, Shh-, Rac- and Notch-dependent transcription/signaling, features in common with human IR-ILC and therefore potential targets for therapy. Gene expression profiling reveals immune infiltration and similarities to a subtype of human Invasive Lobular carcinoma.

2018-10-16 | GSE107432 | GEO

Transcription profiling of human lobular and ductal invasive carcinomas vs normal breast tissue from the same patient to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells

Project description:The aim of our study was to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells. We examined ten mastectomy specimens from postmenopausal breast cancer patients. Ductal and lobular tumor and normal cells were microdissected from cryosections. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. GCOS pairwise comparison algorithm and rank products have identified multiple genes that are differentially expressed in comparisons between ductal and lobular tumor and normal cell types. The results suggest that these genes are involved in epithelial-mesenchymal transition, TGFbeta and Wnt signaling. These changes are present in both tumor types but appear to be more prominent in lobular carcinomas. Ten surgical specimens obtained by mastectomy from postmenopausal patients with invasive ductal (IDC) and lobular breast (ILC) carcinomas were investigated. Of these, 5 were IDCs and 5 were ILCs. Tumor and normal tissues from the same mammary gland were identified by an experienced pathologist, snap-frozen in liquid nitrogen and stored at -80ÂºC for further analysis. Microdissection, RNA isolation, amplification, labeling and microarray analysis are described in sample definitions. Samples from particular cell types (normal ductal, normal lobular, tumor ductal, tumor lobular - 10, 10, 5, 5 samples, respectively) were considered as biological replicates and were compared in between.

2007-11-01 | E-GEOD-5764 | biostudies-arrayexpress

Streptococcus equinus strain:MDC1

Project description:Streptococcus equinus strain:MDC1 Genome sequencing

| PRJNA647691 | ENA

Expression data from invasive lobular carcinoma

Project description:Background: The prognostic value of histologic grade (HG) in invasive lobular carcinoma (ILC) remains uncertain, and most ILC tumors are graded as HG2. Genomic grade (GG) is a 97-gene signature that improves the prognostic value of HG. This study evaluates whether GG may overcome the limitations of HG in ILC. Methods: Gene expression data were generated from frozen tumor samples, and GG calculated according to the expression of 97 genes. The prognostic value of GG was assessed in a stratified Cox regression model for invasive disease-free survival (IDFS) and overall survival (OS).

2016-10-15 | GSE88770 | GEO

MDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis

Project description:MDC1 is a large, modular phospho-protein scaffold that mediates recruitment of signaling and repair complexes to sites of DNA double-strand breaks (DSBs). MDC1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with phosphorylated H2AX (γH2AX), where it recruits downstream factors via direct phosphorylation-dependent protein-protein interactions. Here, using unbiased proteomic analyses we identify a highly conserved protein interaction surface near the MDC1 N-terminus for the DNA damage response protein TOPBP1. We show that TOPBP1 directly binds to two residues in MDC1 that are phosphorylated by CK2. Interestingly, we find that TOPBP1 recruitment to DSBs depends on direct interaction with MDC1 only during mitosis. Furthermore, we demonstrate that disrupting MDC1-TOPBP1 binding causes hypersensitivity to ionizing radiation in mitosis, as well as increased micronuclei and chromosomal instability. Thus, our results highlight an important and hitherto unnoticed function for MDC1 and TOPBP1 in maintaining genome stability during cell division.

2019-03-25 | PXD011850 | Pride

Microarray based gene expression for invasive lobular cancer samples (RATHER)

Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray. Gene expression profiling of 144 ILC breast cancers and 15 ILC cell lines

2016-01-05 | E-GEOD-68057 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data