Expression Data from PtenF341V and Null Mouse Embryonic Fibroblasts
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64302 | GEO | 2014/12/19
SECONDARY ACCESSION(S): PRJNA270711
REPOSITORIES: GEO
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Project description:PTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor mechanisms are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN that differentially alter the Akt axis in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation. These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients Wild type, Pten null and PtenF341V primary mouse embryonic fibroblasts isolated from 13.5 day old embryos (E13.5) were cultured, RNA was extracted and Affymetrix gene expression arrays were performed.
2014-12-19 | E-GEOD-64302 | biostudies-arrayexpress
Project description:PTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor roles are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients Wild type. PtenF341V, PtenWT/null, and Pten null CDH1 positive epithelials cells of mammary ducts from 8 week old female mice were isolated by FACS, RNA was extracted and Affymetrix gene expression arrays were performed.
2014-12-19 | E-GEOD-64303 | biostudies-arrayexpress
Project description:PTEN imparts tumor suppression in mice by cell autonomous and non-autonomous mechanisms. Whether these two tumor suppressor roles are mediated through similar or distinct signaling pathways is not known. Here we generated and analyzed knockin mice that express a series of human cancer-derived mutant alleles of PTEN in either stromal or tumor cell compartments of mammary glands. We find that cell non-autonomous tumor suppression by Pten in stromal fibroblasts strictly requires activation of P-Akt signaling, whereas cell autonomous tumor suppression in epithelial tumor cells is independent of overt canonical pathway activation These findings expose distinct Akt-dependent and independent tumor suppressor functions of PTEN in stromal fibroblasts and tumor cells, respectively, that can be used to guide clinical care of breast cancer patients
2014-12-19 | GSE64303 | GEO
Project description:These experiments aim determine the effects of Pten signaling in fibroblasts on gene expression in other cell compartments in the mammary gland. To achieve this, we used a genetic model in which the tumor suppressor gene Pten was specifically inactivated in stromal fibroblats. We then isolated fibroblasts, epithelial cells and endothelial cells from the mammary glands of mice with either wild type or Pten null fibroblasts. Comparisons were made between wild type and Pten counterparts, not between the various cell types.
2011-12-18 | E-GEOD-24501 | biostudies-arrayexpress
Project description:Oncogenic mutations in tumor cells regulate signaling both within tumor cells and heterotypic stromal cells. However, whether oncogenes regulate tumor cell signaling via stromal cells is poorly understood. Here we show that oncogenic KRAS (KRAS-G12D) uniquely regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with phosphoproteomic multiplexing we conducted a multivariate analysis of heterocellular KRAS-G12D signaling in Pancreatic Ductal Adenocarcinoma (PDA) cells. By engaging heterotypic fibroblasts, KRAS-G12D drives unique reciprocal signaling in tumor cells to employ additional kinases and double the number of regulated signaling nodes from cell-autonomous KRAS-G12D. Heterocellular signaling produces a distinct tumor cell phosphoproteome, total proteome, and increase mitochondria capacity via an IGF1R/AXL-AKT axis. Reciprocal KRAS-G12D phenotypes require a heterocellular context and are unreachable by cell-autonomous KRAS-G12D alone. These results demonstrate oncogene signaling should be viewed as a heterocellular process and our existing homocellular perspective underrepresents the extent of oncogene signaling in cancer.
2016-04-19 | PXD003223 | Pride
Project description:Dysregulation of pre-mRNA alternative splicing (AS) is closely associated with cancers. However, the relationships between the AS and classic oncogenes/tumor suppressors are largely unknown. Here we show that the deletion of tumor suppressor PTEN alters pre-mRNA splicing in its phosphatase-independent manner, and identify262 PTEN-regulated AS events in 293T cells by RNA sequencing, which are associated with significant worse outcome of cancer patients. Based on these findings, we report that nuclear PTEN interacts with the splicing machinery, spliceosome, to regulate its assembly and pre-mRNA splicing. Especially, the exon-2b exclusion of GOLGA2 contributes to PTEN knockdown-induced tumorigenesis by promoting dramatic Golgi extension and secretion, and PTEN depletion significantly sensitizes cancer cells to secretion inhibitors, Brefeldin A and Golgicide A. Given that many cancers lack PTEN expression, our results suggest that Golgi secretion inhibitors alone or in combination with PI3K/Akt kinase inhibitors may be therapeutically useful for PTEN-deficient cancers.
2018-10-18 | PXD009681 | Pride
Project description:PTEN, a widely investigated tumor suppressor, has at least two longer translational variants, PTEN and . However, the regulation and precise roles of endogenous PTEN/ in tumorigenesis remain greatly unknown. Here we show that USP9X and FBXW11 selectively regulate the stability of PTEN/ but not PTEN proteins by deubiqitination and ubiquitination respectively. USP9X promotes and FBXW11 suppresses tumorigenesis mediated by PTEN/. In contrast to the current paradigm for PTEN as a tumor suppressor, PTEN/ promote tumorigenesis of cancer cells in a phosphatase-independent manner. Mechanistically, PTEN/ localized in the nucleus regulate expressions of tumor-promoting genes such as NOTCH3 in the similar way as the H3K4 presenter WDR5. Further, PTEN/ but not PTEN directly interact with WDR5 to promote trimethylation of H3K4 and maintain a tumor-promoting signature. Taken together, our results indicate that PTEN/ are a double-edged sword for carcinogenesis, suggesting that reinterpretation of the importance of PTEN gene in carcinogenesis is warranted.
2019-11-14 | PXD013196 | Pride
Project description:Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor that negatively regulates cell survival and proliferation by antagonizing phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt) signaling. Loss of heterozygosity (LOH) of PTEN, reduced expression of PTEN and overexpression of phosphorylated Akt are frequently found in human gastric cancer, and their changes correlate with tumor progression and prognosis. Previous studies have shown that the deregulated miRNAs in human gastric cancer play important roles in gastric cancer cell proliferation, apoptosis and inflammation. However, miRNAs downstream PTEN/Akt signaling is poorly investigated. To clarify whether PTEN is involved in gastric tumorigenesis, we have generated a gastric epithelium specific PTEN knockout mouse which exhibited gastric tumor formation with enhanced cell proliferation.So the objectives of the microarray experiment were to, a) screen miRNAs which might be regulated by PTEN/Akt signaling by comparing the miRNA expression profiles between PTEN deficient and control gastric epithelia. 2) explore the microRNA mechanism involved in gastric cell proliferation and gastric tumorigenesis. miRNA profiling of mouse gastric epithelium,comparing Pten mutant mouse with controls. 4 samples. Experiments in 2 different time point, 20 days and 60 days after birth, 2 Biological replicates. Mutant tissue vs. controls from mixture of 3-4 mouse.
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Project description:The tumor stroma is believed to contribute to some of the most malignant characteristics of epithelial tumors. However, signaling between stromal and tumor cells is complex and remains poorly understood. Here we show that genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumors. Global gene expression profiling in mammary stromal cells identified a Pten-specific signature associated with massive extra-cellular matrix (ECM) remodeling, innate immune cell infiltraion and increased angiogenesis. Execution of this transcriptional program was mediated, in part, by the induction, phosphorylation and recruitment of Ets2 to target promoters. Remarkably, Ets2 inactivation in Pten stroma-deleted tumors was sufficient to decrease tumor growth and progression. These findings identify the Pten-Ets2 axis as a critical stroma-specific signaling pathway that suppresses mammary epithelial tumors. Experiment Overall Design: Wild type and Pten null primary mammary fibroblasts isolated from 8 week old female mice were cultured, RNA was extracted and Affymetrix gene expression arrays were performed.
2009-11-10 | E-GEOD-16073 | biostudies-arrayexpress
Project description:PTEN is a multifaceted tumor suppressor that is highly sensitive to alterations in expression or function. The PTEN C-tail domain, which is rich in phosphorylation sites, has been implicated in PTEN stability, localization, catalytic activity, and protein interactions, but its role in tumor suppression remains unknown. To address this, we utilized several mouse strains with nonlethal C-tail mutations. Analysis of mice containing nonphosphorylatable or phosphomimetic versions of S380, a C-tail residue hyperphosphorylated in human gastric cancers, reveals that PTEN stability and ability to inhibit PI3K-AKT depends on dynamic phosphorylation-dephosphorylation of this residue. While phosphomimetic S380 drives neoplastic growth in prostate by promoting nuclear accumulation of β-catenin, nonphosphorylatable S380 is not tumorigenic. These data suggest that C-tail hyper-phosphorylation creates oncogenic PTEN and is a potential target for anti-cancer therapy.
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