Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA171714 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We are using the ACI rat model of 17beta-estradiol induced mammary cancer to define the mechanisms through which estrogens contribute to breast cancer development; identify and functionally characterize the genetic variants that determine susceptibility; and define the hormone-gene-environment interactions that influence development of mammary cancer in this physiologically relevant rat model. Female ACI rats are uniquely susceptible to development of mammary cancer when treated continuously with physiologic levels of 17beta-estradiol. Induction of mammary cancer in female ACI rats occurs through a mechanism that is largely dependent upon estrogen receptor-alpha. Interval mapping analyses of progeny generated in intercrosses between susceptible ACI rats and resistant Brown Norway (BN) rats revealed seven quantitative trait loci (QTL), designated Emca3 (Estrogen-induced mammary cancer) through Emca9, each of which harbors one or more genetic determinants of mammary cancer susceptibility. Genes that reside within Emca8 on RNO5 and were differentially expressed between 17beta-estradiol treated ACI and ACI.BN-Emca8 congenic rats were identified as Emca8 candidates.
2013-02-08 | GSE39788 | GEO
Project description:We are using the ACI rat model of 17beta-estradiol induced mammary cancer to define the mechanisms through which estrogens contribute to breast cancer development; identify and functionally characterize the genetic variants that determine susceptibility; and define the hormone-gene-environment interactions that influence development of mammary cancer in this physiologically relevant rat model. Female ACI rats are uniquely susceptible to development of mammary cancer when treated continuously with physiologic levels of 17beta-estradiol. Induction of mammary cancer in female ACI rats occurs through a mechanism that is largely dependent upon estrogen receptor-alpha. Interval mapping analyses of progeny generated in intercrosses between susceptible ACI rats and resistant Brown Norway (BN) rats revealed seven quantitative trait loci (QTL), designated Emca3 (Estrogen-induced mammary cancer) through Emca9, each of which harbors one or more genetic determinants of mammary cancer susceptibility. Genes that reside within Emca8 on RNO5 and were differentially expressed between 17beta-estradiol treated ACI and ACI.BN-Emca8 congenic rats were identified as Emca8 candidates. Two groups of 17beta-estradiol treated female rats were compared. Five ACI and five BN.ACI-Emca8 rats were treated with 17beta-estradiol for 12 weeks. Total RNA was isolated from the mammary glands of these animals, labeled, and hybridized to Affymetrix Rat Genome 230 2.0 Arrays (Affymetrix Inc.). Significantly differentially expressed genes were found between these groups.
2013-02-08 | E-GEOD-39788 | biostudies-arrayexpress
Project description:Genetic susceptibility to mammary carcinogenesis among rat strains
| PRJNA91987 | ENA
Project description:Cancer risk by environmental exposure is modulated by an individual’s genetics and age at exposure. This age-specific period of susceptibility is referred to as a “Window of Susceptibility” (WOS). Radiation exposures poses a high breast cancer risk for women between the early childhood and young adult stage and is reduced in the mid-30s. Rats have a similar WOS for developing breast cancer. Previous studies have identified a looping interaction between a genomic region in the mammary carcinoma susceptibility Mcs5c locus and a known cancer gene, PAPPA. However, the global role of three-dimensional organization in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside WOS. We compared the temporal changes in chromosomal looping to those in expression and find that interactions that have significantly higher counts within WOS are significantly enriched for genes upregulated in WOS. To systematically identify higher-order changes in 3D genome organization, we developed an approach that combines network enhancement to smooth the Hi-C matrices followed by multitask non-negative matrix factorization (NMF) to identify clusters of interacting loci. We found that large-scale topological re-organizations are enriched for differential interactions within and outside the WOS timepoints. Finally, we mapped previously published breast-cancer associated human GWAS variants to rat loci and identified the corresponding rat ortholog gene interacting with the loci. Many of the associated rat genes participate in differential interactions, recapitulate the human SNP- gene interactions and are associated with breast cancer. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may increase susceptibility to breast cancer.
2022-01-11 | GSE184284 | GEO
Project description:Cancer risk by environmental exposure is modulated by an individual’s genetics and age at exposure. This age-specific period of susceptibility is referred to as a “Window of Susceptibility” (WOS). Radiation exposures poses a high breast cancer risk for women between the early childhood and young adult stage and is reduced in the mid-30s. Rats have a similar WOS for developing breast cancer. Previous studies have identified a looping interaction between a genomic region in the mammary carcinoma susceptibility Mcs5c locus and a known cancer gene, PAPPA. However, the global role of three-dimensional organization in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside WOS. We compared the temporal changes in chromosomal looping to those in expression and find that interactions that have significantly higher counts within WOS are significantly enriched for genes upregulated in WOS. To systematically identify higher-order changes in 3D genome organization, we developed an approach that combines network enhancement to smooth the Hi-C matrices followed by multitask non-negative matrix factorization (NMF) to identify clusters of interacting loci. We found that large-scale topological re-organizations are enriched for differential interactions within and outside the WOS timepoints. Finally, we mapped previously published breast-cancer associated human GWAS variants to rat loci and identified the corresponding rat ortholog gene interacting with the loci. Many of the associated rat genes participate in differential interactions, recapitulate the human SNP- gene interactions and are associated with breast cancer. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may increase susceptibility to breast cancer.
2022-01-11 | GSE184280 | GEO
Project description:Anterior pituitary glands were isolated from 21 week old male rats treated for 12 weeks with the synthetic estrogen diethylstilbestrol (DES). Three biological replicates were prepared for each of 4 congenic lines: Ept1, Ept2, Ept6, and Ept9. Congenic rat lines were constructed by introgressing COP alleles onto an ACI background within a given Ept locus. Expression profiles were determined using Affymetrix Rat Genome 230 v. 2.0 arrays. Comparison of congenic rats with the ACI and COP parental strains (see series GSE4028) will allow identification of genes whose expression is influenced by an estrogen-induced pituitary tumor (Ept) QTL. Keywords: Estrogen Response
2006-03-31 | GSE4080 | GEO
Project description:Anterior pituitary glands were isolated from 21 week old male rats treated for 12 weeks with the synthetic estrogen diethylstilbestrol (DES). Three biological replicates were prepared for each of 4 congenic lines: Ept1, Ept2, Ept6, and Ept9. Congenic rat lines were constructed by introgressing COP alleles onto an ACI background within a given Ept locus. Expression profiles were determined using Affymetrix Rat Genome 230 v. 2.0 arrays. Comparison of congenic rats with the ACI and COP parental strains (see series GSE4028) will allow identification of genes whose expression is influenced by an estrogen-induced pituitary tumor (Ept) QTL. Experiment Overall Design: 12 samples from anterior pituitary gland were analyzed. For each of 4 congenic rat lines (Ept1, Ept2, Ept6, Ept9) there were 3 biological replicates of DES-treated male animals. Congenic animals were constructed by introgressing COP alleles onto an ACI background. This was done within the linkage interval for a given Ept locus. These congenic samples can be compared to the ACI and COP parental strains (see GSE4028) to determine expression differences due to a particular chromosomal region, or QTL.
2008-06-12 | E-GEOD-4080 | biostudies-arrayexpress
Project description:Association of Cellular and Molecular Responses in the Rat Mammary Gland to 17beta-Estradiol with Susceptibility to Mammary Cancer
| PRJNA214313 | ENA
Project description:Microarray analysis of rat mammary carcinogenesis
| PRJNA109839 | ENA