Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA125491 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Subtle variations in Pten dose determine cancer susceptibility: Gene expression profiling for MEF cells from a Ptenhy/+ mouse model. We have analyzed the survival and tumor spectrum in a population of Pten ‘hypermorphic’ mice (Ptenhy/+), which express approximately 80% of total Pten protein. Notably, the Ptenhy/+ developed a spectrum of tumors of variable latencies, with breast tumors occurring at the highest penetrance. Surprisingly, all breast tumors analyzed retain two intact copies of Pten, and maintain Pten protein levels above that observed in heterozygosity. Importantly, subtle down-regulation of Pten was found to alter the expression profile of genes involved in cell proliferation. Taken together, our findings support the notion that initiation of tumorigenesis can occur in the absence of genetic hits, thereby questioning the uniqueness of a saltatory model for cancer susceptibility. In order to understand whether subtle variations in Pten level may affect pathways involved in tumorigenesis, we analyzed the genome-wide expression profile of Ptenhy/+ mouse embryonic fibroblasts (MEFs).
2010-02-15 | GSE20316 | GEO
Project description:Subtle variations in Pten dose determine cancer susceptibility: Gene expression profiling for MEF cells from a Ptenhy/+ mouse model. We have analyzed the survival and tumor spectrum in a population of Pten âhypermorphicâ mice (Ptenhy/+), which express approximately 80% of total Pten protein. Notably, the Ptenhy/+ developed a spectrum of tumors of variable latencies, with breast tumors occurring at the highest penetrance. Surprisingly, all breast tumors analyzed retain two intact copies of Pten, and maintain Pten protein levels above that observed in heterozygosity. Importantly, subtle down-regulation of Pten was found to alter the expression profile of genes involved in cell proliferation. Taken together, our findings support the notion that initiation of tumorigenesis can occur in the absence of genetic hits, thereby questioning the uniqueness of a saltatory model for cancer susceptibility. In order to understand whether subtle variations in Pten level may affect pathways involved in tumorigenesis, we analyzed the genome-wide expression profile of Ptenhy/+ mouse embryonic fibroblasts (MEFs). In the Ptenhy/+ mouse model, mice are born with approximately 80% of total Pten protein and are viable and normally fertile. To decrease the expression level of Pten below homozygosity, we targeted intron 3 of Pten with a neomycin (Neo) cassette, under the control of the strong CMV promoter, thereby taking advantage of transcriptional interference. Next, we intercrossed Pten hy/+ mice with Pten+/- mice to generate cohorts of hypomorphic littermate mice with decreasing levels of Pten expression as follows: Ptenwt > Ptenhy/+ > Pten+/- >Ptenhy/- mice littermates. To preserve a constant 129/C57BL/6 mixed genetic background, we have crossed Pten hy/+ mice with Pten +/- for more than seven generations prior to analysis. As expected, Ptenhy/+ mouse embryonic fibroblasts (MEFs) display a level of Pten protein below Ptenwt and above Pten+/- .
2010-02-21 | E-GEOD-20316 | biostudies-arrayexpress
Project description:Decremental loss of PTEN results in cancer susceptibility and tumor progression. In turn this raises the possibility that PTEN elevation might be an attractive option for cancer prevention and therapy. We have generated several transgenic mouse lines with variably elevated PTEN expression levels, taking advantage of BAC (Bacterial Artificial Chromosome)-mediated transgenesis. Super-PTEN mutants are viable and show reduced body size due to decreased cell number, with no effect on cell size. Unexpectedly, PTEN elevation at the organism level results in healthy metabolism characterized by increased energy expenditure and reduced body fat accumulation. Cells derived from these mice show reduced glucose and glutamine uptake, increased mitochondrial oxidative phosphorylation, and are resistant to oncogenic transformation. Mechanistically we find that PTEN elevation orchestrates this metabolic switch by regulating PI3K-dependent and independent pathways, and negatively impacts two of the most pronounced metabolic features of tumor cells: glutaminolysis and the Warburg effect. In order to elucidate the pathophysiological impact of PTEN elevation, we generated transgenic mice carrying additional copies of this critical tumor suppressor gene (referred to as Super-PTEN mice). In order to maintain the regulation properties of the endogenous Pten gene, we made use of large genomic fragments containing the entire Pten locus carried by BACs (Bacterial Artificial Chromosomes). We next generated mouse embryonic fibroblasts (MEFs) and confirmed successful overexpression of PTEN by the BAC transgenic system. Primary cells derived from Super-PTEN mice represent a powerful tool to elucidate the molecular mechanisms underlying dose-dependent PTEN actions. We therefore performed microarray analysis in primary cells (MEFs) derived from day 13.5 embryos obtained by crossing Super-PTEN mice with C57BL6 mice. Three independent embryos from each genotype were analyzed (background: >98%C57BL6 / CBA). Gene expression profile analysis in these cells will reveal target genes and pathways differentially regulated upon PTEN elevation.
2012-12-01 | E-GEOD-35670 | biostudies-arrayexpress
Project description:CNV profiling of tumors obtained from our Chaos3 mouse model for spontaneous breast cancer. The goal of this experiment was to determine copy number variations that were specific to MTs derived from this mouse model, when comapared to non-MTs.
2016-09-14 | GSE81967 | GEO
Project description:Phosphates and tensin homolog (PTEN) is a critical tumor suppressor, and even partial reduction of PTEN levels increases cancer susceptibility. PTEN loss frequently occurs in non-small cell lung carcinoma (NSCLC) and is associated with poor diagnosis. However, there are no effective interventions available to prevent or restore PTEN loss. CREB binding protein (CREBBP or CBP) is a well-known acetyltransferase. PTEN loss in lung cancer carrying CBP loss-of-function (LOF) mutations has not been addressed. Here, we showed that the decreased acetylation of histone deacetylase 3 (HDAC3) due to CBP LOF mutations contributes to PTEN loss in lung cancer. HDAC3 is a member of the class I histone deacetylase family. We found HDAC3 itself is acetylated by CBP at a previously unknown acetylation residue. Our data demonstrated that HDAC3 acetylation is required for gearing down HDAC3 activity and increasing the acetylation of histone proteins to promote the transcription of PTEN. Our findings suggest that HDAC3 acetylation is required for preserving the PTEN expression. The impaired HDAC3 acetylation in CBP LOF mutation lung cancer leads to PTEN loss and consequently promotes tumorigenesis and tumor resistance to chemotherapy. Our findings reveal epigenetic mechanisms of regulating PTEN expression and indicate HDAC3 is a potential target for restoring the tumor suppressor PTEN in CBP LOF mutation cancer.
2024-12-31 | PXD026628 | JPOST Repository
Project description:Yap1 is a critical transcription coactivator in the Hippo pathways. However, its target genes are not well defined in prostate cancer cells. To determine the downstream transcriptional targets and pathways of Yap1 in Pten/Smad4-defiicent mouse prostate cancer cells, ChIP-seq was performed in the Pten/Smad4-deficient mouse prostate cancer cells.
2022-12-31 | GSE162747 | GEO
Project description:It is well-described that the tumor stroma participates in cancer progression, but whether stromal factors can initiate breast tumorigenesis remains unclear. Using our previously described stromal-specific phosphatase and tensin homolog (PTEN) deletion mouse model, we investigated transformative events in young, non-tumor bearing animals. Here, we show stromal PTEN deletion initiates radiation-induced genomic instability on neighboring mammary epithelium through paracrine epidermal growth factor receptor (EGFR) activation. In these mice, a single low dose of whole-body radiation induces mammary hyperplasia, a result that is prevented by pre-treatment with an EGFR inhibitor. We reveal that stromal PTEN is lost in a subset of normal breast samples and is predictive of recurrence in breast cancer patients. Combined, these data suggest both diagnostic and therapeutic chest wall radiotherapy may inadvertently predispose patients with focal stromal PTEN loss to secondary breast cancer, and that this predisposition may be treated prophylactically through EGFR inhibition.
2018-06-13 | GSE93784 | GEO
Project description:Chromosomal translocations or upregulations involving ETS transcription factor are frequent events in prostate cancer pathogenesis and significantly co-occurrence with p53 or PTEN loss. Caused by the low stabilities of ETS proteins in cytosol, mouse models with aberrant expression of wild type ETS transcription factors had subtle phenotypes and only drive prostate cancer progression in the setting of Pten loss. Here we show that prostate specific aberrant expression of mutated ETV4 (V70P71D72-AAA, ETV4-AAA), which is resistence to COP1 mediated protein degradation, results in more stabilized ETV4 protein in mouse prostate. We found that ETV4-AAA mice develop marked prostatic intraepithelial neoplasia (mPin) and p53-dependent cell senescence within 2 weeks, but without tumor development when aged. Interestingly, ETV4-AAA positive cells reduce dramatically in a PTEN loss background, which means that there is no cooperation between ETV4-AAA and PTEN loss. Aberrant ETV4-AAA expression promotes progression of mPin to prostatic adenocarcinoma in a Tp53 deficiency or haploinsufficiency background. In contrast to PTEN loss induced mouse prostate cancers which loss NKX3.1 expression and resistant to castration therapy, these ETV4-AAA tumor cells well maintain AR and NKX3.1 expression and are sensitive to castration therapy.
2021-01-01 | GSE130311 | GEO
Project description:To determine the mechanism underlying the role of VDR in prostatic epitheliales cells during prostate cancer, bulk RNA- sequencing will be performed on sorted luminal cells from PTEN(i)pe-/- and PTEN/VDR(i)pe-/- mouse 1M-3M AGI.
2026-01-12 | GSE281118 | GEO
Project description:To further examine the consequences of Pten loss in a Hedgehog driven, murine FN-RMS, we used microarrays to determine the transcriptomic differences between our aP2-Cre;SmoM2 FN-RMS model (Hatley et al. 2012, Cancer Cell) and aP2-Cre; SmoM2; Pten flox/flox FN-RMSs.
2021-08-24 | GSE166809 | GEO