Expression data from PTEN-deficient regulatory T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE60057 | GEO | 2014/08/05
SECONDARY ACCESSION(S): PRJNA257394
REPOSITORIES: GEO
Similar Datasets
Project description:We used microarrays to assess transcriptional changes in regulatory T cells upon deletion of PTEN. Foxp3+ CD25+ or Foxp3+ CD25- cells were double-sorted from 3 individual healthy 7 week old mice to over 99% purity.
2014-08-05 | E-GEOD-60057 | biostudies-arrayexpress
Project description:KLF5 is a basic transcription factor that regulates multiple biological processes, but its function in tumorigenesis appears contradictory in the current literature, with some studies showing tumor suppressor activity and others showing tumor promoting activity. In this study, we examined the function of Klf5 in prostatic tumorigenesis using mice with prostate specific deletion of Klf5 and Pten, both of which are frequently deleted in human prostate cancer. Histological and molecular analyses demonstrated that when one Pten allele was deleted, which causes mouse intraepithelial neoplasia (mPIN), Klf5 deletion accelerated the emergence and progression of mPIN. When both Pten alleles were deleted, which causes prostate cancer, Klf5 deletion promoted tumor growth and caused more severe morphological and molecular alterations, and homozygous deletion of Klf5 was more effective than hemizygous deletion. Unexpectedly, while Klf5 deletion clearly promoted tumorigenesis in luminal cells, it actually diminished the numbers of Ck5-positive basal cells in the Pten-null tumors. Klf5 deletion also increased the cell proliferation rate in tumors with Pten deletion, which involved extensive activation of the PI3K/AKT and MAPK mitogenic signaling pathways and inactivation of the p15 cell cycle inhibitor. Global gene expression and pathway analyses demonstrated that multiple mechanisms could be responsible for the tumor promoting effect of Klf5 deletion, We used microarrays to detail the global programme of gene expression of Klf5-wildtype and Klf5-null mouse dorsal prostates under Pten-null context to figure out the differential expression profiling underlying tumorigenesis
2014-06-21 | GSE58719 | GEO
Project description:KLF5 is a basic transcription factor that regulates multiple biological processes, but its function in tumorigenesis appears contradictory in the current literature, with some studies showing tumor suppressor activity and others showing tumor promoting activity. In this study, we examined the function of Klf5 in prostatic tumorigenesis using mice with prostate specific deletion of Klf5 and Pten, both of which are frequently deleted in human prostate cancer. Histological and molecular analyses demonstrated that when one Pten allele was deleted, which causes mouse intraepithelial neoplasia (mPIN), Klf5 deletion accelerated the emergence and progression of mPIN. When both Pten alleles were deleted, which causes prostate cancer, Klf5 deletion promoted tumor growth and caused more severe morphological and molecular alterations, and homozygous deletion of Klf5 was more effective than hemizygous deletion. Unexpectedly, while Klf5 deletion clearly promoted tumorigenesis in luminal cells, it actually diminished the numbers of Ck5-positive basal cells in the Pten-null tumors. Klf5 deletion also increased the cell proliferation rate in tumors with Pten deletion, which involved extensive activation of the PI3K/AKT and MAPK mitogenic signaling pathways and inactivation of the p15 cell cycle inhibitor. Global gene expression and pathway analyses demonstrated that multiple mechanisms could be responsible for the tumor promoting effect of Klf5 deletion, We used microarrays to detail the global programme of gene expression of Klf5-wildtype and Klf5-null mouse dorsal prostates under Pten-null context to figure out the differential expression profiling underlying tumorigenesis 4 Klf5-wildtype and 4 Klf5-null mouse (6 months age) dorsal prostates under Pten-null context were used for RNA extraction and hybridization on Affymetrix mouse st 1.0 array
2014-06-21 | E-GEOD-58719 | biostudies-arrayexpress
Project description:The interplay between effector and regulatory T (Treg) cells is crucial for adaptive immunity, but how Treg control effector cell flexibility is elusive. We found that the phosphatase PTEN links Treg stability to the repression of TH1 and TFH (follicular helper) responses. Depletion of PTEN in Treg resulted in excessive TFH and germinal center responses and spontaneous inflammatory disease. These defects are considerably blocked by deletion of Interferon-γ, indicating coordinated control of TH1 and TFH responses. Mechanistically, PTEN maintains Treg stability and proper metabolic balance between glycolysis and mitochondrial fitness. Moreover, PTEN deficiency markedly upregulates mTORC2-Akt activity, and loss of this activity restores PTEN-deficient Treg function. Our studies establish a PTEN-mTORC2 axis that actively maintains Treg stability and coordinates Treg-mediated control of effector cell flexibility. We used microarrays to explore the gene expression profiles differentially expressed in CD4+CD25+Foxp3-YFP+ Treg cells from wild-type (WT; C57BL/6 crossed with Foxp3-Cre) and Ptenfl/flFoxp3-Cre (Ptenfl/fl mice crossed with Foxp3-Cre) mice
2015-01-05 | E-GEOD-63625 | biostudies-arrayexpress
Project description:Hyper-activation of the PI 3-Kinase/ AKT pathway is a driving force of many cancers. Here we identify the AKT-inactivating phosphatase PHLPP1 as a prostate tumor suppressor. We show that Phlpp1-loss causes neoplasia and, upon partial Pten-loss, carcinoma in mouse prostate. This genetic setting initially triggers a growth suppressive response via p53 and the Phlpp2 ortholog, and reveals spontaneous Trp53 inactivation as a condition for full-blown disease. Surprisingly, the co-deletion of PTEN and PHLPP1 in patient samples is highly restricted to metastatic disease and tightly correlated to deletion of TP53 and PHLPP2. These data establish a conceptual framework for progression of PTEN-mutant prostate cancer to life-threatening disease. To better assess the role of Phlpp in prostate we performed micorarray analysis of gene expression in the WT and Pten+/-; Phlpp1-/- mice.
2011-08-16 | E-GEOD-30987 | biostudies-arrayexpress
Project description:T cell-specific deletion of PTEN induces premalignancy in CD4+ CD8+ (DP) immature T cells in the thymus, which progresses to the development of mature CD4+ T cell lymphomas in the lymph nodes and spleen. As part of a screen to identify factors that inhibit progression to malignancy, we compared miRNA expression in premalignant PTEN-deficient DP thymocytes versus wild-type controls. DP thymocytes were collected by cell sorting from three 9-week-old, premalignant T cell-specific PTEN-deficient mice (tPTEN-/-) and three littermate controls. miRNA expression was assessed relative to a reference pool generated from an equal mixture of all samples.
2014-04-12 | E-GEOD-56759 | biostudies-arrayexpress
Project description:T cell-specific deletion of PTEN induces premalignancy in CD4+ CD8+ (DP) immature T cells in the thymus, which progresses to the development of mature CD4+ T cell lymphomas in the lymph nodes and spleen. As part of a screen to identify factors that inhibit progression to malignancy, we compared miRNA expression in premalignant PTEN-deficient DP thymocytes versus wild-type controls.
2014-04-12 | GSE56759 | GEO
Project description:To model the effect of Pten loss on breast cancer, we deleted Pten using a floxed allele and the deleter lines MMTV-Cre(NLST), which targets stem/bi-potent progenitor cells, and WAP-Cre, which targets CD24-positive, pregnancy-identified stem cells/alveolar progenitors. Mammary tumors were detected in WAP-Cre:Ptenf/f females with a latency of 15.2 months. By 18 months, nearly all mice had succumbed to cancer. MMTV-Cre:Ptenf/f mice developed mammary tumors after a longer latency of 26.4 months and reduced penetrance (70%) compared to WAP-Cre:Ptenf/f mice. Tumors from both models were heterogeneous, consisting primarily of differentiated adenocarcinoma (adenomyoepithelioma; ~70%) and adenosquamous carcinoma (20-25%). In addition, a small fraction of tumors was classified as acinar and poorly differentiated adenocarcinoma (4-7%) and adenosarcoma (3-4%). To test the consequences of combined Pten and p53 gene mutation on breast cancer, we deleted both genes via MMTV-Cre or WAP-Cre. Kaplan-Meier tumor free survival curves revealed that WAP-Cre:Ptenf/f:p53f/f and MMTV-Cre:Ptenf/f:p53f/f females developed tumors with reduced latency of 11.3 and 9.8 months, compared with 15.2, 26.4, and 16.9 months for single-mutant WAP-Cre:Ptenf/f, MMTV-Cre:Ptenf/f or MMTV-Cre:p53f/f mice, respectively. In contrast to the heterogeneity of Pten tumors and small percentage of adenosarcomas in these mice, ~70% of Pten:p53 lesions were histologically classified as adeno-sacrcomatoid-like or mesenchymal-like breast cancer, with the rest exhibiting mixed mesenchymal plus adenocarcinomas and differentiated adenocarcinomas. The adeno-sacrcomatoid-like tumors expressed the mesenchymal markers vimentin, K5, SMA, N-cadherin and desmin but not ER, as well as islands of luminal-like K18 expressing cells surrounded by a layer of K14-positive cells. We used microarrays to detect differentially expressed genes in the Pten:p53 double-knock-out vs Pten or p53 single deletions Total RNA was extracted from tumors developed by double Trizol method and hybridized on Affymetrix microarrays.
2012-08-08 | E-GEOD-39955 | biostudies-arrayexpress
Project description:Expression data of PTEN deficient PKO cells
| PRJNA975844 | ENA
Project description:To model the effect of Pten loss on breast cancer, we deleted Pten using a floxed allele and the deleter lines MMTV-Cre(NLST), which targets stem/bi-potent progenitor cells, and WAP-Cre, which targets CD24-positive, pregnancy-identified stem cells/alveolar progenitors. Mammary tumors were detected in WAP-Cre:Ptenf/f females with a latency of 15.2 months. By 18 months, nearly all mice had succumbed to cancer. MMTV-Cre:Ptenf/f mice developed mammary tumors after a longer latency of 26.4 months and reduced penetrance (70%) compared to WAP-Cre:Ptenf/f mice. Tumors from both models were heterogeneous, consisting primarily of differentiated adenocarcinoma (adenomyoepithelioma; ~70%) and adenosquamous carcinoma (20-25%). In addition, a small fraction of tumors was classified as acinar and poorly differentiated adenocarcinoma (4-7%) and adenosarcoma (3-4%). To test the consequences of combined Pten and p53 gene mutation on breast cancer, we deleted both genes via MMTV-Cre or WAP-Cre. Kaplan-Meier tumor free survival curves revealed that WAP-Cre:Ptenf/f:p53f/f and MMTV-Cre:Ptenf/f:p53f/f females developed tumors with reduced latency of 11.3 and 9.8 months, compared with 15.2, 26.4, and 16.9 months for single-mutant WAP-Cre:Ptenf/f, MMTV-Cre:Ptenf/f or MMTV-Cre:p53f/f mice, respectively. In contrast to the heterogeneity of Pten tumors and small percentage of adenosarcomas in these mice, ~70% of Pten:p53 lesions were histologically classified as adeno-sacrcomatoid-like or mesenchymal-like breast cancer, with the rest exhibiting mixed mesenchymal plus adenocarcinomas and differentiated adenocarcinomas. The adeno-sacrcomatoid-like tumors expressed the mesenchymal markers vimentin, K5, SMA, N-cadherin and desmin but not ER, as well as islands of luminal-like K18 expressing cells surrounded by a layer of K14-positive cells. We used microarrays to detect differentially expressed genes in the Pten:p53 double-knock-out vs Pten or p53 single deletions
2012-08-09 | GSE39955 | GEO