Project description:Analysis of MDA-MB-231 breast tumor cell from knocking-down phosphodiesterase 3A (PDE3A), a cyclic nucleotide phosphodiesterase. Results provide insight into the role of PDE3A in breast tumor progression and metastasis.
Project description:Purpose: By catalyzing hydrolysis of cyclic guanosine monophosphate, phosphodiesterase (PDE) 5 is a critical regulator of its concentration and biological effects in different (patho)physiological processes, including cancers. Being PDE5 a known druggable target, we investigated the clinical significance of its expression in breast cancers and the underlying molecular mechanisms by which it may contribute to breast cancer progression. Experimental Design: RT-PCR and immunoblotting analyses were used for PDE5 expression in eight breast cancer cell lines. To examine PDE5âs impact on cancer phenotype, MCF-7 cells, expressing the lowest levels of PDE5, were engineered to stably overexpress PDE5. Cell proliferation was assessed by MTT assays, motility and invasion by wound-healing, transmigration, matrigel-based invasion assays. RNA sequencing identified differentially-expressed genes. Clinical relevance of PDE5 was investigated by immunohistochemistry on tissues and retrospective studies from the Metabric cohort. Results: PDE5 was expressed at lower levels in luminal A-type breast cancer cells (MCF-7) compared to luminal B-like, HER2-overexpressing and basal-like cells. MCF-7 cells stably overexpressing PDE5 exhibited an increased cell motility and invasion through activation of Rho family of GTPases. Treatment of PDE5 clones with selective ROCK or PDE5 inhibitors completely restored the less motile and weak invasive behavior of control cells. In patients, PDE5 expression was found in ~85% of tumor entities analyzed, with the highest intensity staining in high-grade tumors. Retrospective analyses showed that higher PDE5 levels correlated with poorer survival. Conclusion: PDE5 expression enhances breast cancer cell invasive potential, highlighting its role as a novel molecular candidate with prognostic significance and a potential target in the treatment of breast cancers.
Project description:Wnt Phospho protein profiling comparing control and Fto deficient cell after Wnt3a stimulation Control vs Fto deficient MEFs treated with Wnt 3a condioned medium for 40 minutes. 6 replicates per array
Project description:Analysis of mechanism underlying the metabolic effects of ADI-PEG20 at gene expression level. The hypothesis tested in the present study was that ASS1-deficient breast cancer cells would be arginine-auxotrophs and would therefore be sensitive to arginine starvation. Results provide important information of the response of ASS1-deficient breast cancer cells to ADI-PEG20-treatment, such as the suppression of mRNAs encoding mitochondrial respiratory chain proteins.
Project description:Analysis of mechanism underlying the metabolic effects of ADI-PEG20 at gene expression level. The hypothesis tested in the present study was that ASS1-deficient breast cancer cells would be arginine-auxotrophs and would therefore be sensitive to arginine starvation. Results provide important information of the response of ASS1-deficient breast cancer cells to ADI-PEG20-treatment, such as the suppression of mRNAs encoding mitochondrial respiratory chain proteins. Total RNA obtained from ADI-treated, or ADI- and L-arginine-treated 231 cells compared to untreated cells.
Project description:To identify differentially regulated genes between wild-type and Pak1 deficient human breast cancer cells, we performed a comparative gene profiling study by using human whole genome arrays.
Project description:To identify differentially regulated genes between wild-type and Pak1 deficient mouse breast cancer cells, we performed a comparative gene profiling study by using mouse whole genome arrays.
Project description:To identify differentially regulated genes between wild-type and Pak1 deficient mouse breast cancer cells, we performed a comparative gene profiling study by using mouse whole genome arrays. We compared the gene expression profiles of Her2 positive : Pak1 deficient cells vs Her2 positive : Pak1 wild type cells. All the experiments were performed in duplicate using tumor derived cells from two different tumors per group.
Project description:This SuperSeries is composed of the following subset Series: GSE34147: Phosphorylated and SUMO-deficient progesterone receptors drive a gene expression profile important for breast cancer progression (Affymetrix gene expression analysis) GSE34148: Phosphorylated and SUMO-deficient progesterone receptors drive a gene expression profile important for breast cancer progression (Illumina gene expression analysis) Refer to individual Series