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MCF10A cells in 3-D culture for 15 h after treatment with CtIP-RNAi vs Luc-RNAi adenovirus

ABSTRACT: BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. A dozen of genes including angiopoietin-1 (ANG1), a secreted angiogenic factor, are co-repressed by BRCA1 and CtIP based on microarray analysis of mammary epithelial cells in 3-D culture. BRCA1, CtIP and ZBRK1 form a complex that coordinately represses ANG1 expression via a ZBRK1 recognition site in ANG1 promoter. Impairment of this complex upregulates ANG1, which stabilizes endothelial cells forming capillary-like network structure. Consistently, Brca1-deficient mouse mammary tumors exhibit accelerated growth, pronounced vascularization and overexpressed ANG1. These results suggest, besides its role in maintaining genomic stability, BRCA1 directly regulates the expression of angiogenic factors to modulate the tumor microenvironment. Keywords: MCF10A, human mammary epithelial cells, 3-D Matrigel, 15 h, CtIP-RNAi

ORGANISM(S): Homo sapiens

PROVIDER: GSE4751 | GEO | 2006/05/02

SECONDARY ACCESSION(S): PRJNA104543

REPOSITORIES: GEO

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RNAi knock down of human breast cancer cell line MCF10A with BCRA1 or CtIP-RNAi reveals removal of the BRCA1/CtIP/ZBRK1 repressor complex on ANG1 promoter leads to accelerated mammary tumor growth contributed by prominent vasculature

Project description:BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. A dozen genes, including angiopoietin-1 (ANG1), a secreted angiogenic factor, are corepressed by BRCA1 and CtIP based on microarray analysis of mammary epithelial cells in 3D culture. BRCA1, CtIP, and ZBRK1 form a complex that coordinately represses ANG1 expression via a ZBRK1 recognition site in the ANG1 promoter. Impairment of this complex upregulates ANG1, which stabilizes endothelial cells that form a capillary-like network structure. Consistently, Brca1-deficient mouse mammary tumors exhibit accelerated growth, pronounced vascularization, and overexpressed ANG1. These results suggest that, besides its role in maintaining genomic stability, BRCA1 directly regulates the expression of angiogenic factors to modulate the tumor microenvironment.

2007-10-26 | E-GEOD-4754 | biostudies-arrayexpress

MCF10A cells in 3-D culture for 15 h after treatment with BRCA1-RNAi vs Luc-RNAi adenovirus

2006-05-02 | GSE4750 | GEO

Transcription profiling of human MCF10A cells in 3-D culture for 15 h after treatment with CtIP-RNAi vs Luc-RNAi adenovirus

Project description:BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. A dozen of genes including angiopoietin-1 (ANG1), a secreted angiogenic factor, are co-repressed by BRCA1 and CtIP based on microarray analysis of mammary epithelial cells in 3-D culture. BRCA1, CtIP and ZBRK1 form a complex that coordinately represses ANG1 expression via a ZBRK1 recognition site in ANG1 promoter. Impairment of this complex upregulates ANG1, which stabilizes endothelial cells forming capillary-like network structure. Consistently, Brca1-deficient mouse mammary tumors exhibit accelerated growth, pronounced vascularization and overexpressed ANG1. These results suggest, besides its role in maintaining genomic stability, BRCA1 directly regulates the expression of angiogenic factors to modulate the tumor microenvironment. Experiment Overall Design: MCF10A cells seeded at 5x105 cells/60mm plate were infected with adenoviral luciferase- or CtIP-RNAi in duplicate at 20 MOI for 24h. Infected cells were re-seeded at 5x105 cells in a 60mm plate pre-coated with Growth Factor Reduced Matrigel and covered with the growth medium containing 2% Matrigel at 37Â°C for 15h. RNA was extracted and quality assessed. cDNA synthesized from the harvested RNA was biotin-labeled, hybridized onto Affymetrix HG U133 PLUS 2.0 array (54,676 genes) and stained with streptavidin-phycoerythrin. The hybridized array was analyzed using GeneChipÂ® Scanner 3000 and GCOS 1.2 software (Affymetrix) at the UCI Microarray Core service.

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RNAi profiling of human MCF10A cells in 3-D culture for 15 h after treatment with BRCA1-RNAi vs Luc-RNAi adenovirus

Project description:BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. A dozen of genes including angiopoietin-1 (ANG1), a secreted angiogenic factor, are co-repressed by BRCA1 and CtIP based on microarray analysis of mammary epithelial cells in 3-D culture. BRCA1, CtIP and ZBRK1 form a complex that coordinately represses ANG1 expression via a ZBRK1 recognition site in ANG1 promoter. Impairment of this complex upregulates ANG1, which stabilizes endothelial cells forming capillary-like network structure. Consistently, Brca1-deficient mouse mammary tumors exhibit accelerated growth, pronounced vascularization and overexpressed ANG1. These results suggest, besides its role in maintaining genomic stability, BRCA1 directly regulates the expression of angiogenic factors to modulate the tumor microenvironment. Experiment Overall Design: MCF10A cells seeded at 5x105 cells/60mm plate were infected with adenoviral luciferase- or BRCA1-RNAi in duplicate at 20 MOI for 24h. Infected cells were re-seeded at 5x105 cells in a 60mm plate pre-coated with Growth Factor Reduced Matrigel and covered with the growth medium containing 2% Matrigel at 37Â°C for 15h. RNA was extracted and quality assessed. cDNA synthesized from the harvested RNA was biotin-labeled, hybridized onto Affymetrix HG U133 PLUS 2.0 array (54,676 genes) and stained with streptavidin-phycoerythrin. The hybridized array was analyzed using GeneChipÂ® Scanner 3000 and GCOS 1.2 software (Affymetrix) at the UCI Microarray Core service.

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2019-11-12 | PXD014441 | Pride

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Effects of the expression of M1775R and A1789T BRCA1 missense variants on the transcriptome of HeLa cells

Project description:BRCA1 (breast cancer 1, early onset) mutations confer a high breast and ovarian cancer risk. Most of BRCA1 cancer-predisposing mutations originate truncated proteins, but missense mutations have also been detected in familial breast and ovarian cancer patients. These variants are rare and their role in cancer predisposition is often difficult to ascertain. Our purpose in the present work was to study the molecular mechanisms affected in human cells by two BRCA1 missense variants both located in the second BRCA1 BRCT domain, M1775R and A1789T. These variants were isolated from familial breast cancer patients and their role in the pathogenesis of breast cancer was also investigated by a study previously performed by our group in yeast cells. Here we present a microarray study to compare the expression profiles of HeLa cells transfected with these two variants and HeLa cells transfected with BRCA1 wild type. Data analysis was performed by evaluating three comparisons: M1775R versus wild-type (M1775RvsWT-contrast), A1789T versus wild-type (A1789TvsWT-contrast) and the mutated BRCT domain versus wild-type (MutvsWT-contrast), obtained by considering the two variants as a unique BRCT mutation. We found 173 differentially expressed genes in MutvsWT-contrast, 201 in M1775RvsWT-contrast and 313 in A1789TvsWT-contrast. Our results showed that the considered BRCA1 variants had an impact on cell processes often deregulated in cancerogenesis, such as cell cycle progression and DNA damage response and repair. Thus, our study further supports the putative role in the pathogenesis of cancer of the M1775R and A1789T BRCA1 variants from a molecular point of view.

2012-06-01 | E-MTAB-761 | biostudies-arrayexpress

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