The transcriptional regulator c-Myc is the most frequently deregulated oncogene in human tumors. Targeted overexpression of this gene in mice results in distinct types of lung adenocarcinomas. By using microarray technology, alterations in the expression of genes were captured based on a female transgenic mouse model in which, indeed, c-Myc overexpression in alveolar epithelium results in the development of bronchiolo-alveolar carcinoma (BAC) and papillary adenocarcinoma (PLAC).
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Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors.
Specimen part, Disease, Disease stage
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Specimen part
View SamplesThe satellite cell of skeletal muscle provides a paradigm for quiescent and activated tissue stem cell states. We have carried out transcriptome analyses by comparing satellite cells from adult skeletal muscles, where they are mainly quiescent, with cells from growing muscles, regenerating (mdx) muscles, or with cells in culture, where they are activated. Our study gives new insights into the satellite cell biology during activation and in respect with its niche.
An adult tissue-specific stem cell in its niche: a gene profiling analysis of in vivo quiescent and activated muscle satellite cells.
Specimen part
View SamplesWe used microarrays to identify Pax3 targets during myogenesis in the mouse embryo
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Specimen part
View SamplesWe used microarrays to identify Pax3 targets during myogenesis in the mouse embryo
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Specimen part
View SamplesThe LIM-only protein FHL2 acts as a transcriptional modulator that positively or negatively regulates multiple signaling pathways. We recently reported that FHL2 cooperates with CBP/p300 in the activation of -catenin/TCF target gene cyclin D1. In this paper, we demonstrate that FHL2 is associated with the cyclin D1 promoter at the TCF/CRE site, providing evidence that cyclin D1 is a direct target of FHL2. We show that deficiency of FHL2 greatly reduces the proliferative capacity of spontaneously immortalized mouse fibroblasts which is associated with decreased expression of cyclin D1 and p16INK4a, and hypophosphorylation of Rb. Reexpression of FHL2 in FHL2-null fibroblasts efficiently restores cyclin D1 levels and cell proliferative capacity, indicating that FHL2 is critical for cyclin D1 activation and cell growth. Moreover, ectopic cyclin D1 expression is sufficient to override growth inhibition of immortalized FHL2-null fibroblasts. Gene expression profiling revealed that FHL2 deficiency triggers a broad change of the cell cycle program that is associated with downregulation of several G1/S and G2/M cyclins, E2F transcription factors and DNA replication machinery, thus correlating with reduced cell proliferation. This change also involves downregulation of the negative cell cycle regulators, particularly INK4 inhibitors, which could counteract the decreased expression of cyclins, allowing cells to grow. Our study illustrates that FHL2 can act on different aspects of the cell cycle program to finely regulate cell proliferation.
The LIM-only protein FHL2 regulates cyclin D1 expression and cell proliferation.
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View SamplesTo determine the modulation of gene expression of mouse BMDCs in the presence of living intracellular Leishmania amazonensis amastigotes
Sorting of Leishmania-bearing dendritic cells reveals subtle parasite-induced modulation of host-cell gene expression.
Sex, Age
View SamplesIn mammals, resident dermal macrophages (Ms) are subverted by Leishmania (L.) amazonensis amastigotes as host cells permissive for parasite multiplication. These Leishmania are living within a communal parasitophorous vacuole (PV) and are expected to trigger unique M transcriptional signatures. We performed a transcription profiling of mouse Ms harboring amastigotes to get insights into their reprogramming as host cells for parasite multiplication. BALB/c mouse bone marrow-derived Ms were either loaded or not with four amastigotes on average. Twenty four hours later, when amastigotes multiply, total RNA from M cultures was prepared, amplified and hybridized onto Affymetrix Mouse430_2 GeneChips. The outcome recorded a total of 1,248 probe-sets showing significant differential expression. Comparable fold-change values for a handful of genes were obtained between Affymetrix technology and the more sensitive RTqPCR method. Ingenuity Pathway Analysis software pinpointed the up-regulation of the sterol biosynthesis pathway (P-value = 1.31e-02) involving several genes (1.95 to 4.30 fold-change values), and the modulation of various genes involved in polyamine synthesis and in pro/counter-inflammatory signaling. Our findings suggest that amastigotes exploit the M lipid and polyamine pathways to multiply efficiently, and induce a counter-inflammatory environment to expand their dermis niche.
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Sex, Specimen part, Cell line, Treatment
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