Following androgen ablation treatment for advanced prostate cancer, almost all men relapse after a period of initial response to therapy, which eventually is life threatening. We have previously found that purine-rich element binding protein, PUR alpha, was significantly repressed in androgen-independent prostate cancer cell lines in comparison to an androgen-dependent line. Moreover, over-expressing PURa in androgen-independent prostate cancer cells attenuated their cell proliferation. The aim of the studies described here was to uncover some of the mechanisms by which over-expression of PURa attenuates cell proliferation.
Purine-rich element binding protein (PUR) alpha induces endoplasmic reticulum stress response, and cell differentiation pathways in prostate cancer cells.
No sample metadata fields
View SamplesInsulin resistance is the hallmark of obese and type 2 diabetes patients. Defective insulin sensitivity in the liver results in increased glucsoe production, which is the major cause of hyperglycemia in diabetic patients. Increased lipopolysaccharide (LPS) leakage from the gut of diet-induced obesity causes insulin resisitance; moreover, activation of deacetylase Sirtuin1 restore insulin sensitivity in obesity. However, the mechanism resulting in insulin resistance by LPS remains poorly understood. Here, we show that Ep300 (P300) harboring an intrinsic acetyltransferase activity was rapidly induced in the liver of animals fed a high-fat diet, and the induction of Ep300 is through LPS-stimulated activation of ER stress. Induced Ep300 impairs insulin signaling by acetylating mediators in insulin signaling. Inhibition of P300 acetyltransferase activity improves insulin signaling. Thus, Ep300 acetyltransferase activity is a therapeutic target.
No associated publication
Sex, Age, Specimen part
View SamplesExposure to genotoxic stresses such as cosmic radiation and second-hand tobacco smoke may increase the risk of breast cancer formation. Towards an understanding of how exposure to these genotoxic agents affect breast cancer biogenesis, we have shown that treating non-tumorigenic immortalized breast MCF 10A cells with low doses (0.1 Gray) of radiation as well as cigarette smoke condensate can generate a neoplastic breast cancer phenotype. The transformed phenotype promoted increased mammosphere numbers, altered cell cycle phases, and increased invasion and motility. In addition, exclusion of Hoechst 33342 dye, a surrogate marker for increased ABC transporters, was observed, which indicates a possible increase in drug resistance. Furthermore, differential gene expression profiles were generated from the individual and combination treatment. Overall, the results indicate that when normal breast cells are exposed to low dose radiation in combination with cigarette smoke condensate a phenotype is generated that exhibits traits indicative of neoplastic transformation. Taken together, these results provide a new insight into a possible etiology for breast cancer formation in individuals exposed to cosmic radiation and second-hand smoke.
No associated publication
Cell line
View SamplesAverage life expectancy for patients with metastatic melanoma is less than 6 months, and only a handful of treatment options are available. If the disease can be stopped before it spreads to other organs, life expectancy is greatly increased. The goal of this project is to identify possible regulators of melanoma metastasis by determining genes whose expression is modulated when the cells are grown in contact with endothelial cells. Identification of genes involved in this cell-cell communication could have therapeutic implications.
Integration of genotypic and phenotypic screening reveals molecular mediators of melanoma-stromal interaction.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization.
Sex, Specimen part
View SamplesTranscriptional profiles of Fz4-/- retinal endothelial cells were compared to that of wild type endothelial cells under various culture conditions. The goal was to identify the transcriptional response to Frizzled 4 signaling in cultured retinal endothelial cells. To analyze the Norrin response of WT and Fz4-/- retinal endothelial cells in culture, we co-cultured these cells either with HEK293 cell line that stably expresses Norrin or with control 293 cells.
No associated publication
Sex, Specimen part
View SamplesAndrogenetic alopecia (AGA) or common baldness results from a marked decrease in hair follicle size. This miniaturization may be related to loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from the same individuals for the presence of hair follicle stem and progenitor cells using flow cytometry to quantitate cells expressing CYTOKERATIN 15 (KRT15), CD200, CD34 and ALPHA-6-INTEGRIN (ITGA6). High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. Cells with the highest level of KRT15 expression were maintained in bald scalp; however, distinct populations of CD200high ITGA6high cells and CD34-positive cells were markedly diminished. Consistent with a progenitor cell phenotype, the diminished populations localized closely to the stem-cell rich bulge area but were larger and more proliferative than the bulge stem cells. In functional assays, analogous CD200 high /Itga6 high cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings suggest that a defect in stem cell activation plays a role in the pathogenesis of AGA.
Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells.
Sex, Age, Specimen part
View SamplesWe were interesed in defining the gene signautre of volar skin.
To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease.
No sample metadata fields
View SamplesTo characterize the long-term effect on the transcriptome of a decrement in Norrin/Fz4/Lrp signaling, microarray hybridization was performed with RNA from acutely dissociated and anti-PECAM immunoaffinity-purified adult WT, Fz4-/-, Lrp5-/-, and Norrin- retinal vascular cells.
No associated publication
Sex, Specimen part
View SamplesGenetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct hepatic gene expression profiles between Keap1 knockout and triterpenoid treated mice
No associated publication
Sex, Age, Specimen part
View Samples