Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide analysis of BRCA1 and PALB2 [RA stimulation]

ABSTRACT: Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity. MCF-7 cells were infected with PALB2, BRCA1 and non targeting (SCR) shRNAs. After puromycin selection, cells were stimulated with 10microM Retinoic Acid (RA) for 24 hours

ORGANISM(S): Homo sapiens

SUBMITTER: Alessandro Gardini

PROVIDER: E-GEOD-45714 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Genome-wide analysis of BRCA1 and PALB2 [TNF-alpha stimulation]

Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity. MCF-7 cells were infected with PALB2, BRCA1, p65/RelA and non targeting (SCR) shRNAs. After puromycin selection, cells were stimulated with 10ng/ml TNF-alpha 1 hour

2013-09-30 | E-GEOD-45713 | biostudies-arrayexpress

Genome-wide analysis of BRCA1 and PALB2 [ChIP-seq and RNA-seq]

Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity. Comparison of the genome wide profiles of the BRCA protein complex (BRCA1 and PALB2) and phosphorylated RNAPII (P-Ser2) in MCF10A cells by ChIP-seq. Effect of BRCA1 and PALB2 knockdown (shRNAs) on transcription was assessed by RNA-seq.

2013-09-30 | E-GEOD-40591 | biostudies-arrayexpress

Genome-wide analysis of BRCA1 and PALB2 [ChIP-seq and RNA-seq]

2013-09-30 | GSE40591 | GEO

Genome-wide analysis of BRCA1 and PALB2 [RA stimulation]

2013-09-30 | GSE45714 | GEO

Genome-wide analysis of BRCA1 and PALB2 [TNF-alpha stimulation]

2013-09-30 | GSE45713 | GEO

A BRCA1 coiled-coil domain variant disrupting PALB2 interaction predisposes to mammary tumors with a targetable defect in homologous recombination repair [CNV-seq]

Project description:The BRCA1 tumor suppressor gene encodes a multi-domain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks (DSBs), which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, BRCA1 missense variants affecting its PALB2-interacting coiled-coil domain are considered sequence variants of uncertain clinical significance (VUS). Using genetically engineered mice, we now show that a BRCA1 coiled-coil domain VUS, Brca1 p.L1363P, disrupting the interaction with PALB2 leads to embryonic lethality and loss of breast cancer suppression. Brca1 p.L1363P mammary tumors develop with a similar latency as Brca1-null tumors, but show different histopathological features and more stable DNA copy number profiles. Nevertheless, Brca1 p.L1363P mammary tumors are HRR-incompetent and responsive to cisplatin and PARP inhibition.

2022-02-01 | GSE182449 | GEO

A BRCA1 coiled-coil domain variant disrupting PALB2 interaction predisposes to mammary tumors with a targetable defect in homologous recombination repair [RNA-seq]

2022-02-01 | GSE182448 | GEO

aCGH analysis of Palb2GT/+;p53-/- and Palb2+/+;p53-/- lymphomas

Project description:Palb2 interacts with BRCA1 and BRCA2 in supercomplexes involved in DNA repair via homologous recombination. Heterozygous germline mutations in PALB2 confer a moderate risk of breast cancer while biallelic PALB2 mutations are linked to a severe form of Fanconi anaemia characterized by early childhood solid tumours and severe chromosomal instability. In contrast to BRCA1- or BRCA2-associated cancers, breast tumours in heterozygous PALB2 mutation carriers do not show loss of the wild type allele, suggesting PALB2 might be haploinsufficient for tumour suppression. To study the role of PALB2 in development and tumourigenesis, we have generated Palb2GT mouse mutants using a gene trap approach. Whereas Palb2GT/GT homozygous mutant embryos died at mid-gestation due to massive apoptosis, Palb2GT/+ heterozygous mice were viable and did not show any obvious abnormalities. Deletion of p53 alleviated the phenotype of Palb2GT/GT embryos, but did not rescue embryonic lethality. In addition, loss of p53 did not significantly collaborate with Palb2 heterozygosity in tumourigenesis in heterozygous or homozygous p53 knockout mice. Tumours arising in Palb2GT/+;p53+/– or Palb2GT/+;p53–/– compound mutant mice retained the wild type Palb2 allele and did not display increased genomic instability. Comparison of 15 Palb2GT/+;p53-/- and 11 Palb2+/+;p53-/- lymphomas. Spleen/liver DNA of the same animal was used as reference material.

2011-01-21 | E-GEOD-26723 | biostudies-arrayexpress

TUSC4 functions as a tumor suppressor by regulating BRCA1’s stability via the E3 ubiquitination pathway

Project description:Expression of the tumor suppressor protein BRCA1 is frequently lost in breast cancer patients, and the loss of its expression is associated with disruption of various critical functions in cells and cancer development. In the present study, we demonstrated that microarray analysis of cells with tumor suppressor candidate 4 (TUSC4) knockdown indicated critical changes such as cell cycle, cell death pathways and a global impact to cancer development. More importantly, we observed a clear cluster pattern of TUSC4-knockdown gene profiles with established homologous recombination (HR) repair defect signature. Additionally, TUSC4 protein can physically interact with E3 ligase Herc2 and prevents BRCA1 degradation via ubiquitination pathway. Knockdown of TUSC4 expression enhanced BRCA1 polyubiquitination, leading to BRCA1 protein degradation and a marked reduction in HR repair efficiency. Notably, ectopic expression of TUSC4 effectively suppressed the proliferation, invasion, and colony formation of breast cancer cells in vitro and tumorigenesis in vivo. Furthermore, knockdown of TUSC4 expression transformed normal mammary epithelial cells and enhanced the sensitivity of U2OS cells to the treatment of poly(ADP-ribose) polymerase inhibitors. Therefore, TUSC4 may act as a bona fide tumor suppressor by regulating BRCA1 protein stability and function in breast cancer. Two groups of samples are included: 1.U2OS-shcontrol 2.U2OS-shTUSC4 knockdown. Gene expression profiles of U2OS-shTUSC4 cells were compared to that of parental U2OS-shcontrol cells.

2014-08-21 | E-GEOD-60535 | biostudies-arrayexpress

aCGH analysis of Palb2GT/+;p53-/- and Palb2+/+;p53-/- lymphomas

2011-01-21 | GSE26723 | GEO