The jmjC-domain containing H3K4 histone demethylase JARID1B/KDM5B/PLU1 is over-expressed in human breast cancer and is a potential target for breast cancer treatment. To investigate the in vivo function of JARID1B, we developed a new strain of Jarid1b knockout mice and characterized the phenotypes in detail. Unlike previously reported knockout strains, the majority of our Jarid1b knockout mice are viable beyond embryonic and neonatal stages. Nonetheless, these mice exhibit decreased body weight, higher incidence of adult mortality and decreased female fertility. Furthermore, Jarid1b knockout mice show delayed mammary gland development. Mechanistically, loss of JARID1B leads to decreased serum estrogen levels and reduced proliferation of mammary epithelial cells in early puberty. In addition, in mammary epithelial cells, loss of JARID1B diminishes the expression of key regulators of mammary morphogenesis, including FOXA1, estrogen receptor (ER), and GATA3. Taken together, these results indicate that JARID1B positively regulates mammary ductal development through both extrinsic and cell-autonomous mechanisms.
Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes.
Specimen part
View SamplesUsing microarray analysis, we explored the differences in gene expression in wounded and intact skin using murine model. Injured skin samples were examined at days 1 and 4 post injury.
Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate.
Specimen part, Time
View Samplestumor microenviroment facilitates metastatic spread by eliciting reversible changes in the phenotypes of cancer cells
Mesenchymal stem cells within tumour stroma promote breast cancer metastasis.
No sample metadata fields
View SamplesTranscriptome profiling studies suggest that a large fraction of the genome is transcribed and many transcripts function independent of their protein coding potential. The relevance of noncoding RNAs (ncRNAs) in normal physiological processes and in tumorigenesis is increasingly recognized. Here, we describe consistent and significant differences in the distribution of sense and antisense transcripts between normal and neoplastic breast tissues. Many of the differentially expressed antisense transcripts likely represent long ncRNAs. A subset of genes that mainly generate antisense transcripts in normal but not cancer cells is involved in essential metabolic processes. These findings suggest fundamental differences in global RNA regulation between normal and cancer cells that might play a role in tumorigenesis. Overall design: Global strand-specific transcriptome profilings of 2 samples in cancer and 1 sample in normal from clinical breast tissue using asymmetrical strand-specific analysis of gene expression (ASSAGE).
Altered antisense-to-sense transcript ratios in breast cancer.
No sample metadata fields
View SamplesWe used microarrays to detail the global programme of gene expression in embryonic stem cells, early differentiated embrioid bodies and effect of short-term ATRA treatment.
Activation of retinoic acid receptor signaling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Cell line
View SamplesThe two most common melanoma histopathologic subtypes, superficial spreading (SSM) and nodular melanoma (NM), are believed to represent sequential phases of linear progression from radial to vertical growth. Studies suggest, however, that SSM and NM are biologically distinct. We utilized an integrative genomic approach to examine the possibility that SSM and NM are the result of independent pathways characterized by unique molecular alterations. Cell lines including SSM, NM, metastatic melanoma, and melanocyte controls were evaluated for copy number changes and differential mRNA expression using single nucleotide polymorphism array (SNP 6.0, Affymetrix) and gene array (U133A 2.0, Affymetrix). Data sets were integrated to identify copy number alterations that correlated with gene expression, and array results were validated using immunohistochemistry on human tissue microarrays (TMAs) and an external data set. The functional effect of genomic deletion was assessed by lentiviral overexpression. Integrative genomics revealed 8 genes in which NM/SSM-specific copy number alterations were correlated with NM/SSM differential gene expression (P<0.05, Spearmans rank). Pathways analysis of differentially expressed genes (N=114) showed enrichment for metabolic-related processes. SSM-specific genomic deletions (DIS3, MTAP, G3BP2, SEC23IP, USO1) were verified in an expanded panel of cell lines, and forced overexpression of MTAP in SSM resulted in reduced cell growth. Metabolism-related gene ALDH7A1 was verified as overexpressed in NM using human TMAs.The identification of recurrent genomic deletions in SSM not present in NM challenges the linear model of melanoma progression and supports the unique molecular classification of SSM and NM.
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Cell line
View SamplesA small number of tumor-derived cell lines have formed the mainstay of cancer therapeutic development, yielding drugs with impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics, and more readily understand their potential clinical impact, we constructed a functional metabolic portrait of 46 independently-derived breast tumorigenic cell lines, contrasted with purified normal breast epithelial subsets, freshly isolated pleural effusion breast tumor samples and culture-adapted, non-tumorigenic mammary epithelial cell derivatives. We report our analysis of glutamine uptake, dependence, and identification of a significant subset of triple negative samples that are glutamine auxotrophs. This NCBI GEO submission comprises a small datasest generated to compare the expression profiles of the above nontumorigenic, purified normal and purified pleural effusion samples with 10 established breast cancer-derived cell lines. This dataset was subsequently merged with a previously published expression dataset derived from 45 independent breast cancer derived cell lines (Neve, et al 2006), and analyses contrasting various subsets of the merged dataset were published.
Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target.
Specimen part, Cell line
View SamplesmRNA expression was assayed from T47D SCR and T47D EGLN2 conditional knock down cell lines in order to profile the gene expression pattern regulated by EGLN2.
Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase.
Specimen part, Cell line
View SamplesUtilizing M. musculus as a model of mitochondrial dysfunction provides insight into cellular adaptations which occur as a consequence of genetic alterations causative of human disease. We characterized genome-wide expression profiles of liver-conditional knockout mice for Pdss2 compared with loxP controls.
Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease.
No sample metadata fields
View Samples