Analysis of the transcriptional profiles of mRNA and microRNA in Rasless fibroblasts. 4-Hydroxy-tamoxifen (4-OHT) treatment triggers removal of K-Ras expression in [H-Ras-/-;N-Ras-/-;K-Raslox/lox;RERTert/ert ] mouse fibroblasts (named K-Raslox) generating Rasless MEFs which are unable to proliferate, but recover proliferative ability after ectopic expression of constitutively active downstream kinases such as BRAF and MEK1.
Reversible, interrelated mRNA and miRNA expression patterns in the transcriptome of Rasless fibroblasts: functional and mechanistic implications.
Specimen part, Cell line, Treatment
View SamplesThe specific ablation of Rb1 gene in stratified epithelia (RbF/F;K14cre) promotes proliferation and altered differentiation but is insufficient to produce spontaneous tumors. The pRb relative, p107, compensates some of the functions of pRb in these tissues, however RbF/F;K14cre;p107-/- mice die postnatally. Acute pRb loss in stratified epithelia, using an inducible mouse model (RbF/F;K14creERTM), shows that p107 exerts specific tumor suppressor functions in its absence. After simultaneous absence of pRb and p107, p53 transcriptional function is impaired and Pten expression is reduced. All mutant mice develop spontaneous squamous tumors carcinomas rapidly. Gene expression analysis of mouse tumors, besides supporting the impaired p53 function and the susceptibility to Akt/mTOR inhibitors, also revealed significant overlap with human squamous carcinomas. Thus, RbF/F;K14creERTM;p107-/- may constitute a new mouse model for these malignancies. Collectively, these data demonstrate the existence of a previously unreported functional connection between pRb, Pten and p53 tumor suppressors, through p107, of a particular relevance in squamous tumor development.
A novel tumor suppressor network in squamous malignancies.
Specimen part
View SamplesA permantly active form of the oncogene Akt was expressed in the keratinocytes of the basal proliferative layer of the epidermis. Stem cells of the hair follicle expressing the cell surface marker CD34 were isolated. RNA form the CD34(+) and CD34(-) keratinocytes was extracted and and hybridized to Mouse Genome 430 2.0 Affymetrix arrays.
Akt signaling leads to stem cell activation and promotes tumor development in epidermis.
Specimen part
View SamplesType I Interferons encompasses a large family of closely related cytokines comprising of at least 13 IFN- isotypes and single IFN-. Both IFN- and IFN- exert their activity through a common receptor IFNAR. Type I Interferons have broad regulatory effects and various subtypes of dendritic cells are influenced by this cytokines. In our study we asked question whether the low, constitutive levels of type I Interferons produced under steady state conditions are important for proper function of splenic conventional dendritic cells.
Absence of IFN-beta impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70.
Sex, Age, Specimen part
View SamplesThe epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies. To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy. Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.
Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy.
Age, Specimen part
View SamplesThe goal of this project was to characterize DCs from lymphopenic mice, like RAG (recombination activated gene) deficient mice and to examine the influence of mature B and T cells on the antigen presenting ability of splenic cDCs. We demonstrate how cellular cross-talk can shape the character and function of cDCs. Lymphopenic conditions, where splenic cDCs have to develop and differentiate, drastically change their character and their ability to cross-present soluble antigen.
Immunoglobulins drive terminal maturation of splenic dendritic cells.
Sex, Age, Specimen part
View SamplesmicroRNA miR-144/451 is highly expressed during erythropoiesis. We deleted the miR-144/451 gene locus in mice and compared the transcriptomes of miR-144/451-null bone marrow erythroid precursors to stage-matched wild-type control cells.
miR-451 protects against erythroid oxidant stress by repressing 14-3-3zeta.
Specimen part
View SamplesIn order to explore molecules whose expression is controlled by Slc39a13, we investigated gene expression profiling of primary osteoblast isolated from wild-type and Slc39a13 knockout mice.
The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.
No sample metadata fields
View SamplesMurine prostate epithelial cells (PECs) were obtained from Ccnd1-/- and Ccnd1+/+ FvB mice (2-3 months of age). RNA extracted from PECs (3 technical replicates for each group) was labeled and used to probe Affymetrix 430_2.0 arrays.
Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells.
No sample metadata fields
View SamplesmiR-155 transgenic mice develop pre-B cell leukemia/lymphoma. Though some targets of miR-155 are known, understanding of the mechanism by which miR-155 overexpression drives malignant transformation is not known. MicroRNAs regulate multiple genes.
miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the Eμ-miR-155 transgenic mouse model.
No sample metadata fields
View Samples