Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA97475 | ENA |
REPOSITORIES: ENA
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Project description:We mated mice with floxed alleles of both Apc and Pten, to mice with floxed alleles for Arid1a, to obtain female mice with both copies of all three genes floxed. At 7 to 8 weeks of age the right ovarian bursal cavites of the mice were injected with 50 million plaque-forming units of adenovirus expressing Cre recombinase, which causes the floxed genes to be knocked out. Tumor tissue from 3 mice for each group was obtained at necropsy, RNA purified, and targets for Affymetrix arrays synthesized from the mRNAs. We used Affymetrix Mouse Genome 430 2.0 arrays, which hold 45101 probe-sets. Raw data was processed with Robust Multi-array Average algorithm (RMA). Data is log2-transformed transcript abundance estimates. We performed T-tests to compare the 3 vs 3 arrays. We supply a supplementary excel workbook that holds the same data as the data matrix file, but also holds the probe-set annotation at the time we analyzed the data, and some very simple statistical calculations, which select subsets of the probe-sets as differentially expressed. Consumers should consider obtaining more up-to-date probe-set annotation for the array platform. We have also supplied a second supplementary tar archive holding software and files to 1) perform permutation testing of the probe-set selection in order to estimate false discovery rates for the probe-sets we selected as differentially expressed, 2) perform enrichment testing of GO terms, and 3) to perform enrichment testing of KEGG pathways and 3000 curated gene sets from version 4 of the Molecular Signatures Database (MSigDB). The software is in "C". Ovarian endometrioid carcinoma samples from 3 female mice with conditional knockout of Apc and Pten, were compared to similar tumors from 3 female mice with conditional knockout of Apc, Pten, and Arid1a.
2015-08-04 | E-GEOD-67695 | biostudies-arrayexpress
Project description:Effects of Arid1a knockout in murine ovarian endometrioid carcinomas with biallelic inactivation of Apc and Pten
| PRJNA280703 | ENA
Project description:We treated 6-8 week old mice that had floxed alleles of both Apc and Pten (for both alleles in each case) that also carry an Ovgp1-iCre-ERT2 transgene, with one of two treatments; a third group received neither treatment. The Ovgp1-iCre-ERT2 expresses Cre recombinase fused to a tamoxifen-inducible fragment of the estrogen receptor, in tissues where the Ovgp1 gene (oviductal glycoprotein 1) is expressed, which is almost exclusively in mouse oviductal epithelium (equivalent to human fallopian tube epithelium = FTE). Treating the mice with tamoxifen permits the Cre recombinase to enter the cell nucleus and inactivate the Apc and Pten genes. Six of the mice were treated with intraperitoneal injection of tamoxifen (0.1g/kg of body weight) dissolved in corn oil on days 1 and 3 and developed oviductal tumors (OdT) yielding 6 of the samples. Four mice (yielding 5 samples) were instead injected with 50 million plaque-forming units of replication-incompetent AdCre into both ovarian bursal cavities on day 1, which inactivated Apc and Pten in the ovarian surface epithelium (OSE), and lead to ovarian tumors (OT). Ovaries were also harvested from four untreated 6-8 week old mice with the same genotype, with two ovaries from each mouse comprising one control sample. RNA was purified from tumor or normal tissue, and targets for Affymetrix arrays synthesized from the mRNAs. We used Affymetrix Mouse Gene 2.1 ST arrays, which hold 41345 probe-sets, but we largely analyzed just those 25216 probe-sets that were mapped to Entrez gene IDs. Raw data was processed with Robust Multi-array Average algorithm (RMA). Data is log2-transformed transcript abundance estimates. We fit a one-way ANOVA model to the three groups of samples. We supply a supplementary excel workbook that holds the same data as the data matrix file, but also holds the probe-set annotation at the time we analyzed the data, and some simple statistical calculations, which select subsets of the probe-sets as differentially expressed. Consumers should consider obtaining more up-to-date probe-set annotation for the array platform. We also provide supplementary excel files that show our simple analysis of GSE6008, which consists of 99 human ovarian tumor samples of 4 types, and 4 normal ovary samples, where we fit an ANOVA model to the 5 groups. In yet another supplementary file we show the correlation between each human tumor and mouse tumor, where we correlate the difference in log2-transformed values of each tumor from the average of the normals for the same species, for just those genes that were 1-to-1 best homologs according to build 68 of NCBI's Homologene, in order to see how much the human tumors resemble the mouse tumors. Six oviductal tumor samples from 6 mice with conditional knockout of Apc and Pten driven by an Ovgp1-iCre-ERT2 transgene , 5 ovarian tumor samples from 4 mice with conditional knockout of Apc and Pten driven by injection of AdCre into both ovarian bursal cavities, and 4 normal ovary samples from 4 mice.
2016-08-25 | E-GEOD-80085 | biostudies-arrayexpress
Project description:Overexpression and/or amplification of the ErbB-2 oncogene, as well as inactivation of the tumor suppressor PTEN, are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the MMTV promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (MMTV-NIC). Disruption of PTEN in the mammary epithelium of the MMTV-NIC model system dramatically accelerated the formation of multifocal and highly metastatic mammary tumors, which exhibit homogenous pathology. PTEN-deficient/NIC tumorigenesis was associated with an increase in angiogenesis. Moreover, inactivation of PTEN in the MMTV-NIC mouse model resulted in hyperactivation of the PI3K/Akt signalling pathway. However, like the parental strain, tumors obtained from PTEN-deficient/NIC mice displayed histopathological and molecular features of the luminal-like subtype of breast cancer. Taken together, our findings provide important implications in understanding the molecular determinants of mammary tumorigenesis driven by PTEN deficiency and ErbB-2 activation, and could provide a valuable tool for testing the efficacy of therapeutic strategies that target these critical signalling pathways. Experiment Overall Design: Common reference design. 9 samples (including 2 normal tissue and 7 tumor tissue samples) replicated twice as dye swaps, generating a total of 18 arrays.
2009-07-03 | E-GEOD-13916 | biostudies-arrayexpress
Project description:A profile of gene expression differences in mouse small intestine with short term induction of Apc inactivation, in the presence and absence of additional mutations in combinations of Kras, Pik3ca, Pten, and Slc7a5.
2024-07-19 | GSE272639 | GEO
Project description:Overexpression and/or amplification of the ErbB-2 oncogene, as well as inactivation of the tumor suppressor PTEN, are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the MMTV promoter to directly couple expression of activated ErbB-2 and Cre recombinase to the same mammary epithelial cell (MMTV-NIC). Disruption of PTEN in the mammary epithelium of the MMTV-NIC model system dramatically accelerated the formation of multifocal and highly metastatic mammary tumors, which exhibit homogenous pathology. PTEN-deficient/NIC tumorigenesis was associated with an increase in angiogenesis. Moreover, inactivation of PTEN in the MMTV-NIC mouse model resulted in hyperactivation of the PI3K/Akt signalling pathway. However, like the parental strain, tumors obtained from PTEN-deficient/NIC mice displayed histopathological and molecular features of the luminal-like subtype of breast cancer. Taken together, our findings provide important implications in understanding the molecular determinants of mammary tumorigenesis driven by PTEN deficiency and ErbB-2 activation, and could provide a valuable tool for testing the efficacy of therapeutic strategies that target these critical signalling pathways.
2009-06-29 | GSE13916 | GEO
Project description:Preclinical modeling of epithelial ovarian cancer in immune competent mice progressing to spontaneous tumors is challenging, requiring multiple genetic modifications in the host. We have generated a total of 28 immortalized cell lines with distinct genetic traits. Primary OSE cells were propagated in vitro and reached immortalization after an average of 8-10 months in culture. The cells were further engineered via deletion of Trp53, activation of oncogenic KrasG12D, deletion of Pten tumor suppressor or KrasG12D/Pten-/- combination. Cellular transformation was confirmed in vivo, via orthotopic tumor growth syngeneic hosts. Two different Trp53 null cell lines recapitulate high grade serous histology, Pten deletion triggers aggressive, high grade endometrioid tumors, and cells with dual KrasG12D activation and Pten deletion model carcinosarcoma. The cells express different tumor antigens, secrete various levels of chemoattracting cytokines and chemokines and trigger diverse in vivo inflammation profiles, including intratumoral T and B lymphocyte conglomerates. RNAseq data from 16 cell lines reveal the gene expression profile of several distinct models for high grade serous, endometrioid and carcinosarcoma histotypes. This versatile collection of murine cell lines significantly broadens the preclinical modeling capacity in ovarian cancer.
2023-07-01 | GSE232055 | GEO
Project description:We use RNAseq to examine gene expression changes in braf;pten mouse melanomas after arising after conditional genetic inactivation of ezh2
2021-12-29 | GSE192491 | GEO
Project description:Transcriptional profiling of mouse prostate tumors with conditional mutations in the Pten, Apc, or Tgfbr2 genes
| PRJNA422241 | ENA
Project description:We thought the immediate effects of APC inactivation may represent unexplored therapeutic vulnerabilities in later stages of advanced colorectal adenocarcinoma. We performed transcriptome profiling of epithelial colon organoids immediately after APC inactivation and cross-referenced gene expression changes to the transcriptomes of several mouse models of colon cancer, including colon tumors in an inflammation-induced CRC model (AOM-DSS), a model of familial adenomatous polyposis (FAP, the Apcmin mouse), and an implantation-based model of metastatic adenocarcinoma using Apc/Trp53/KrasG12D/Smad4 quadruple-mutant tumor organoids15 (APKS tumoroids). Of the roughly 150 genes whose expression is acutely induced upon APC loss and remains elevated in these colon cancer models.
2022-12-31 | GSE198758 | GEO