Combined gene expression and DNA occupancy profiling identifies JAK/STAT signaling as a valid therapeutic target of t(8;21) AML
Combined gene expression and DNA occupancy profiling identifies potential therapeutic targets of t(8;21) AML.
Specimen part
View SamplesFLT3-ITDs Introduce a Myeloid Differentiation and Transformation Bias in Lympho-myeloid Multipotent Progenitors
FLT3-ITDs instruct a myeloid differentiation and transformation bias in lymphomyeloid multipotent progenitors.
Sex, Specimen part
View SamplesBRCA1, a well-known breast and ovarian cancer susceptibility gene with multiple interacting partners, is predicted to have diverse biological functions. However, to date its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate risk variant, and found that it does not impair DNA damage repair but abrogates the repression of miR-155, a bona fide oncomir. We further show that in the absence of functional BRCA1, miR-155 is up-regulated in BRCA1-deficient mouse mammary epithelial cells, human and mouse BRCA1-deficienct breast tumor cell lines as well as tumors. Mechanistically, we found that BRCA1 represses miR-155 expression via its association with HDAC2, which deacetylates H2A and H3 on the miR-155 promoter. Finally, we show that over-expression of miR-155 accelerates whereas the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Taken together, our findings demonstrate a new mode of tumor suppression by BRCA1 and reveal miR-155 as a potential therapeutic target for BRCA1-deficient tumors.
Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
Specimen part
View SamplesWe examined the functional significance of the R1699Q variant of human BRCA1 gene using a mouse ES cell-based assay.
Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
Specimen part
View SamplesFrom preliminary experiments, HSP70 deficient MEF cells display moderate thermotolerance to a severe heatshock of 45.5 degrees after a mild preshock at 43 degrees, even in the absence of hsp70 protein. We would like to determine which genes in these cells are being activated to account for this thermotolerance.
Microarray analysis of cellular thermotolerance.
No sample metadata fields
View SamplesTo identify a cohort of rhythmically expressed genes in the murine Distal Colon,microarrays were used to measure gene expression over a 24-hour light/dark cycle.The rhythmic transcripts were classified according to expression patterns, functions and association with physiological and pathophysiological processes of the colon including motility, colorectal cancer formation and inflammatory bowel disease.
Transcriptional profiling of mRNA expression in the mouse distal colon.
No sample metadata fields
View SamplesComparative analysis of gene expression in cultured primary keratinocytes isolated from newborn control (K14-cre; GPx4fl/+) and knockout (K14-cre; GPx4fl/fl) mice.
Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2.
Specimen part
View SamplesImmortalized, amelanotic melanocytes isolted from skin of Balb/c express enzymatically-inactive tyrosinase due to a homozygous point mutation (TGT->TCT) in tyrosinase gene, resulting in a lack of melanin . To serve as a control cell line, pigmentation was restored in these cells by correcting the point mutation using an RNA-DNA oligonucleotide (kingly gift from Dr. Alexeev Y. Vitali).
Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Treatment
View SamplesWe examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally.
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Treatment
View Samples