Comparison of WapCre;Rank;Brca1;p53 and WapCre;Brca1;p53 mouse primary mammary tumors
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71362 | GEO | 2017/02/12
SECONDARY ACCESSION(S): PRJNA291043
REPOSITORIES: GEO
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Project description:Gene expression profiles of "spontaneous" and transplanted topotecan-resistant BRCA1;P53-deficient mammary tumors and their matched untreated controls
2010-01-05 | E-NCMF-28 | biostudies-arrayexpress
Project description:We compared the expression levels of X-linked genes in the mammary glands of Brca1ï11/ï11p53+/- mutant and control (p53+/-) mice at three different stages of the mammary cycle: virgin, pregnant day 16.5, and lactation day 1, using a cDNA microarray. In about 690 X-linked genes that are expressed at these three stages of mammary cycle of development, we found 16 X-linked genes showed altered expression levels in Brca1ï11/ï11p53+/- mammary glands in comparison with controls at all three time points. Among them, 9 genes were up-regulated and 7 were down-regulated. This result indicates that mutation of Brca1 could affect expression of a few X-linked genes in mammary tissues. However, this was unlikely caused by failure of X chromosome inactivation, as seven of them were down-regulated, and Xist RNA was expressed in all the Brca1 mutant mammary tissues. Experiment Overall Design: Mutations in breast cancer associated gene-1 (BRCA1) are associated with hereditary breast and ovarian cancers. BRCA1 encodes a tumor suppressor protein that functions in DNA repair, transcriptional regulation, chromatin remodeling, centrosome duplication and checkpoint control, etc.. We were interested in fishing out the genes regulated by Brca1. Three pairs of mammary glands from Brca1ï11/ï11p53+/- mutant and control (p53+/-) mice at three different stages of the mammary cycle were analyzed by microarray for gene expression levels.
2008-06-14 | E-GEOD-5861 | biostudies-arrayexpress
Project description:We have studied in vivo responses of spontaneous Brca1- and p53-deficient mouse mammary tumors to treatment with doxorubicin, docetaxel or cisplatin.
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Project description:Rank overexpression attenuates mammary tumorigenesis by inducing senescence in mammary epithelial cells but enhances tumor aggressiveness by increasing stemness.
2022-02-24 | GSE139675 | GEO
Project description:Brca1 mutation predisposes women to early onset of breast and ovarian cancers.Through its diverse functions in DNA damage repair, cell cycle control, transcription regulation, ubiquitination and so on, BRCA1 acts as a very significant tumor suppressor and genomic safeguard. Brca1 deficiency induces severe cellular stress, when occurring in the mammary glands, it impairs the regular developmental process and eventually causes tumorigenesis due to accumulation of genome instability and other mechanisms. The Brca1-defiencient mouse mammary tumor were characterized with great tumoral heterogeneity, which is in line with the human breast cancers carrying BRCA1 mutations. Here we studied the molecular complexicity of Brca1-deficient mouse mammary tumors vie RNA sequencing.
2021-11-17 | GSE148565 | GEO
Project description:We compared the expression levels of X-linked genes in the mammary glands of Brca1 D11/D11;p53+/- mutant and control (p53+/-) mice at three different stages of the mammary cycle: virgin, pregnant day 16.5, and lactation day 1, using a cDNA microarray. In about 690 X-linked genes that are expressed at these three stages of mammary cycle of development, we found 16 X-linked genes showed altered expression levels in Brca1 D11/D11;p53+/- mammary glands in comparison with controls at all three time points. Among them, 9 genes were up-regulated and 7 were down-regulated. This result indicates that mutation of Brca1 could affect expression of a few X-linked genes in mammary tissues. However, this was unlikely caused by failure of X chromosome inactivation, as seven of them were down-regulated, and Xist RNA was expressed in all the Brca1 mutant mammary tissues. Keywords: BRCA1 mutation analysis
2006-09-19 | GSE5861 | GEO
Project description:Breast cancers that are “triple-negative” for the clinical markers ESR1, PGR, and HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53, and Brca1 pathways are each associated with triple-negative and Basal-like subtypes. Our mouse genetic studies demonstrate that the combined inactivation of Rb and p53 pathways is sufficient to suppress the physiological cell death of mammary involution. Furthermore, concomitant inactivation of all three pathways in mammary epithelium has an additive effect on tumor latency and predisposes highly penetrant, metastatic adenocarcinomas. The tumors are poorly differentiated and have histologic features that are common among human Brca1-mutated tumors, including heterogeneous morphology, metaplasia, and necrosis. Gene expression analyses demonstrate that the tumors share attributes of both Basal-like and Claudin-low signatures, two molecular subtypes encompassed by the broader, triple-negative class defined by clinical markers. These studies establish a unique animal model of aggressive forms of breast cancer for which there are no effective, targeted treatments. Rb, p53, and Brca1 are associated with inherited forms of cancer, but defects in these pathways are also found together in a subset of breast cancer patients without a family history of the disease. Simultaneous inactivation of all three pathways causes more aggressive disease than do pair-wise combinations, indicating that the pathways play non-overlapping roles in tumor prevention. We investigated the effect of perturbation of Rb family pathways, p53, and/or Brca1 in mouse mammary epithelium. Eighteen tumors were compared to normal spleen DNA.
2012-09-18 | E-GEOD-40925 | biostudies-arrayexpress
Project description:Breast cancers that are “triple-negative” for the clinical markers ESR1, PGR, and HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53, and Brca1 pathways are each associated with triple-negative and Basal-like subtypes. Our mouse genetic studies demonstrate that the combined inactivation of Rb and p53 pathways is sufficient to suppress the physiological cell death of mammary involution. Furthermore, concomitant inactivation of all three pathways in mammary epithelium has an additive effect on tumor latency and predisposes highly penetrant, metastatic adenocarcinomas. The tumors are poorly differentiated and have histologic features that are common among human Brca1-mutated tumors, including heterogeneous morphology, metaplasia, and necrosis. Gene expression analyses demonstrate that the tumors share attributes of both Basal-like and Claudin-low signatures, two molecular subtypes encompassed by the broader, triple-negative class defined by clinical markers. These studies establish a unique animal model of aggressive forms of breast cancer for which there are no effective, targeted treatments. Rb, p53, and Brca1 are associated with inherited forms of cancer, but defects in these pathways are also found together in a subset of breast cancer patients without a family history of the disease. Simultaneous inactivation of all three pathways causes more aggressive disease than do pair-wise combinations, indicating that the pathways play non-overlapping roles in tumor prevention.
2011-12-17 | GSE34479 | GEO
Project description:The dire need for more effective treatments for clinically aggressive breast cancers has motivated intensive investigations into their cellular and molecular etiology. Breast cancers that are “triple-negative” for the clinical markers, ESR1, PGR, and HER2, typically belong to the Basal-like molecular subtype. Defective Rb, p53, and Brca1 pathways are each associated with triple-negative and Basal-like subtypes. Our mouse genetic studies demonstrate that concomitant inactivation of all three pathways in mammary epithelium has an additive effect on tumor latency, and predisposes highly penetrant, metastatic, adenocarcinomas. These tumors are poorly differentiated with histologic features that are common among human Brca1-mutated tumors, including heterogeneous morphology, metaplasia, and necrosis. Transcriptomic analyses demonstrated that the tumors shared attributes of both Basal-like and Claudin-low signatures, two molecular subtypes encompassed by the broader triple-negative category defined by clinical markers. Ex vivo tumorsphere formation, which was suppressed by Notch and Wnt pathway inhibition, and tumor antigen profiles and are consistent with enrichment of stem-like and luminal progenitor cells among these tumors. These studies establish a novel mouse model of malignant breast cancer based on events in the human disease and underscore the non-reciprocal requirements of three canonical tumor suppressor pathways in breast cancer evolution. Morphogenetic pathways may provide additional avenues for targeted therapeutic intervention. Gene expression analysis of mouse mammary tumors with perturbation of Rb family pathways, p53, and/or Brca1 are compared to other mouse model tumors (n=152)
2011-12-17 | E-GEOD-34479 | biostudies-arrayexpress
Project description:BRCA1 mutation-carriers are predisposed to develop Basal-like breast cancer (BLBC), and p53 mutations are present in the majority of human BLBC cases, suggesting loss of these two tumor suppressors play key roles in development of BLBC. Recent studies suggest that the majority of human breast cancers, including BLBC, may originate from mammary epithelial cells (MECs) in the luminal lineage. However, how loss of p53 and BRCA1 contributes to development of BLBC from luminal MECs remains largely elusive. We developed a novel genetic targeting and lineage tracing approach based on intraductal injection of Cre-expressing adenovirus under the control of the pan-luminal Keratin 8 (K8) promoter (Ad-K8-Cre). We performed intraductal injection of Ad-K8-Cre to female mice carrying conditional knockout alleles of Brca1 and Trp53. The injected females developed mammary tumors within 12 months after injection. Microarray expression profiling of these tumors showed that they most closely resembled human BLBC.
2019-06-27 | GSE114787 | GEO