Overcoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-Ras-V12-induced senescence. Mechanistically, a PAK4 – RELB - C/EBPa axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Se151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPa. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition. Overall design: We quantify transcription via high-throughput RNA sequencing in two human breast cancer cell lines (BT-549 and Hs578T) 72hrs after transient transfection with control (siControl) or PAK4-targetting siRNA.
PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer.
Specimen part, Cell line, Subject
View SamplesUsing a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Macrophage responses to silica nanoparticles are highly conserved across particle sizes.
No sample metadata fields
View SamplesWe performed a transcriptomic analysis of Pi-starvation and recovery after resupplying Pi in Arabidopsis thaliana (Columbia-0) wild type plants and double mutant spx1,spx2. Results show that SPX1 is a Pi-dependent inhibitor of the transcription factor PHR1, a central regulatory protein in the control of transcriptional responses to Pi starvation.
SPX1 is a phosphate-dependent inhibitor of Phosphate Starvation Response 1 in Arabidopsis.
Age, Specimen part
View SamplesHuman prostate cancer tissues analyses
In silico dissection of cell-type-associated patterns of gene expression in prostate cancer.
No sample metadata fields
View SamplesPulmonary alveoli are complex architectural units thought to undergo endogenous or pharmacologically induced programs of regeneration and degeneration. To study the molecular mechanism of alveoli loss mice were calorie restricted at different timepoints. Lungs were harvested and processed for RNA extraction.
Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression.
Time
View SamplesIt has been shown that dexamethasone (Dex) impairs the normal lung septation that occurs in the early postnatal period. Treatment with retinoic acid (ATRA) abrogates the effects of Dex. To understand the molecular basis for the Dex indiced inhibition of the formation of the alveoli and the ability of ATRA to prevent the inhibition of septation, gene expression was analyzed in 4-day old mice treated with diluent (control), Dex-treated and ATRA+Dex-treated.
DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation.
No sample metadata fields
View SamplesConditional IRF8 KO mice (mice with a conditional allele of Irf8 crossed with CD19-Cre mice) showed increased numbers of both Gene expression data spleen marginal zone (MZ) and Gene expression data spleen follicular (FO) B cells compared to control mice.
IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools.
No sample metadata fields
View SamplesU87-EV human glioblastoma xenograft tumours is therapeutically treated by bevacizumab, a humanized anti-human VEGF mAb, or dibenzazepine (DBZ) when tumour is established in BALB/c SCID mice. At the end point, collect tumour samples and extracted total RNA for microarray to investigate the gene profile changes compared to control. These include the genes from human tumour cells and mouse host stroma cells.
A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.
Specimen part
View SamplesU87-EV human glioblastoma xenograft tumours is therapeutically treated by bevacizumab, a humanized anti-human VEGF mAb, or dibenzazepine (DBZ), when tumour is established in BALB/c SCID mice. At the end point, collect tumour samples and extracted total RNA for microarray to investigate the gene profile changes compared to control. These include the genes from human tumour cells and mouse host stroma cells.
A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.
Specimen part
View SamplesU87-EV human glioblastoma xenograft tumours is therapeutically treated by bevacizumab, a humanized anti-human VEGF mAb, when tumour is established in BALB/c SCID mice. At the end point, collect tumour samples and extracted total RNA for microarray to investigate the gene profile changes compared to control. These include the genes from human tumour cells and mouse host stroma cells.
A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.
Cell line
View Samples