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Prevention of mammary tumor progression by silencing HoxA1 via intraductal injection of nanoparticle-formulated siRNA

ABSTRACT: Silencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression. 8 week wild type FVB mouse whole mammary gland and 8week to 20 week transgenic FVB C3(1)-SV40Tag mouse whole mammary gland

ORGANISM(S): Mus musculus

SUBMITTER: Hu Li

PROVIDER: E-GEOD-50813 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Silencing HoxA1 by intraductal injection of siRNA lipidoid nanoparticles prevents mammary tumor progression in mice.

Brock Amy A Krause Silva S Li Hu H Kowalski Marek M Goldberg Michael S MS Collins James J JJ Ingber Donald E DE

Science translational medicine 20140101 217

With advances in screening, the incidence of detection of premalignant breast lesions has increased in recent decades; however, treatment options remain limited to surveillance or surgical removal by lumpectomy or mastectomy. We hypothesized that disease progression could be blocked by RNA interference (RNAi) therapy and set out to develop a targeted therapeutic delivery strategy. Using computational gene network modeling, we identified HoxA1 as a putative driver of early mammary cancer progress ...[more]

PMID: 24382894

Similar Datasets

Prevention of mammary tumor progression by silencing HoxA1 via intraductal injection of nanoparticle-formulated siRNA

Project description:Silencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression.

2013-12-31 | GSE50813 | GEO

Genome wide DNA methylation analysis of C3(1) SV40TAg mouse model of breast cancer

Project description:Genome-wide screen for aberrant DNA methylation in mammary gland tumors of the C3(1) Sv40Tag mouse model of breast cancer in comparison with wildtype mammary glands.

2018-02-22 | GSE77096 | GEO

Multi-omics integration analysis of spontaneous breast intraductal papilloma of the tree shrew

Project description:In this study, a novel MS method, Data-independent Acquisition (DIA) was utilized, which has high specificity and coverage, to perform protein quantitation and find out differentially expressed proteins between spontaneous breast intraductal papilloma and mammary gland tissue; and the biological functions and regulatory pathways of target protein were enriched by GO enrichment and KEGG enrichment analysis.

2020-08-25 | PXD021121 |

Identification of Hoxa1 downstream targets

Project description:To better understand the role of Hoxa1 during embryogenesis and gain insight to the transcriptional network controlled by this gene, we carried out a large-scale screening for Hoxa1 downstream targets by performing microarray analysis. Tissue from the rhombomere 3-5 region of wildtype and Hoxa1 null embryos, including neuroectoderm, mesoderm and otic ectoderm was microdissected at the peak of Hoxa1 expression. RNA from wildtype and Hoxa1Δ/Δ samples was hybridized to the Agilent mouse whole genome array.

2011-09-03 | GSE25868 | GEO

Modeling myelodysplastic syndromes in mice by altered Hoxa1 spliceform expression

Project description:The homeobox gene, Hoxa1, has two different isoforms generated by alternative splicing: a full-length homeodomain-containing Hoxa1 (Hoxa1-FL), and a truncated Hoxa1 (Hoxa1-T), that lacks the homeodomain. Oncoretroviral overexpression of wildtype Hoxa1 cDNA (WT-Hoxa1), which generates both Hoxa1 isoforms, in murine hematopoietic stem and progenitor cells (HSPCs) perturbed hematopoiesis, resulting in myelodysplastic syndromes (MDS) in mice. Overexpression of a mutated Hoxa1 cDNA (MUT-Hoxa1) that generates Hoxa1-FL but not Hoxa1-T led to a more severe MDS capable of transforming to secondary acute myeloid leukemia (sAML). Similar to human MDS, DNA damage repair pathways were downregulated in Hoxa1-overexpressing hematopoietic progenitor cells. Conditional knock-in mouse models revealed a Hoxa1-FL dosage-dependent effect on MDS disease severity. Our data reveal that increased expression of Hoxa1-FL in HSPCs is sufficient to initiate MDS in mice. CD34+ cells from up to 50% of patients with MDS had elevated HOXA1-FL expression, highlighting the clinical relevance of our mouse models.

2023-11-28 | GSE62853 | GEO

Modeling myelodysplastic syndromes in mice by altered Hoxa1 spliceform expression (CMP)

2023-11-28 | GSE227775 | GEO

Hoxa1 LoF RNA-seq

Project description:Transcriptomic profiling of Hoxa1 null mouse embryos

2023-02-28 | GSE224217 | GEO

Expression data from C3(1)Tag mammary tumors, tumor derived cell line (M6) and normal mammary tissue (FVB)

Project description:M6 cells expression a similar genetic signature as the parent tumor, C3(1)Tag tumor. The mammary tumors, and tumor cell line, are distinct from normal mammary epithelial tissue (FVB) BRCA/p53, cmyc, h2n, p53ERneg, p53ERpos, pymt and ras samples were not reported in this paper. We used microarrays to determine whether the M6 cell line retains the SV40Tag signature (91 gene signature) that is expressed in C3(1)Tag tumors but not FVB normal mammary tissue.

2011-08-31 | E-GEOD-25488 | biostudies-arrayexpress

Identification of Hoxa1 downstream targets

2011-09-02 | E-GEOD-25868 | biostudies-arrayexpress