The relationships between cancer cells and the microenvironment play a critical role in cancer growth and development. The bone stroma consists of mesenchymal stem cells (MSCs) and mature osteoblasts that promote cancer growth. Yet it is not completely understood what are the molecular processes guiding cancer cells progression to the bone. In this study, a co-culture assay and subsequent gene profiling arrays were used to compare the gene expression profile of a pre-osteoblastic cell line (MBA-15) with that of a mammary adenocarcinoma (DA3) cells. Following co-culture, cells were separated by magnetic beads based on the expression of CD326 antigen. RNA was purified and hybridized on gene expression array. The gene expression pattern changes were followed by qRT-PCR. We demonstrate that co-cultured DA3 cells express elevated levels of genes that regulate growth and responses to both hormonal stimulus and wounding, as well as reduced expression of genes related to lipid metabolism. Also, co-cultured pre-osteoblastic cells showed reduced expression of cell-junction genes. The study presents a simplified model system, composed of pre-osteoblastic and mammary cancer cells, that potentially mimics the molecular interactions in the tumor microenvironment which contribute to tumor-progression.
Molecular profiling of functional interactions between pre-osteoblastic and breast carcinoma cells.
Specimen part, Cell line
View SamplesLipid metabolic disarray in young and adult mice offspring's liver is induced by saturated fatty acids (SFA) but prevented by alpha linolenic acid (ALA, 18:3 3) in the maternal diet during pregnancy and lactation. The aim of the present study was to analyse the impact of maternal dietary ALA on the liver gene expression in the new-born offspring in comparison to a SFA diet. Methods: C57Bl6/J dams were fed with diets normal in calories but rich in ALA or SFA before mating and during pregnancy. Pups were sacrificed at birth and liver parameters were assessed. Gene expression was characterized by microarray analysis and validated by real time qPCR. Results: ALA compared to SFA in maternal diets during pregnancy, increased polyunsaturated fatty acids while differentially modified fatty acid desaturase activities in offspring liver. Overall, 474 and 662 genes from born pups liver, were differentially regulated by ALA and SFA compared to control diet (p<0.05; Fold change 2), respectively. Notably, Per3 was up-regulated by ALA whereas down-regulated by SFA, compared to control diet. Conclusions: ALA and SFA enriched diets differentially affect gene expression pattern in the offsprings liver. ALA in particular, upregulates genes associated to low adiposity.
Maternal Diet Enriched with α-Linolenic or Saturated Fatty Acids Differentially Regulates Gene Expression in the Liver of Mouse Offspring.
Specimen part, Disease, Treatment
View SamplesAccumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis- multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/ Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.
eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling.
Specimen part, Cell line, Treatment
View SamplesThe bundle sheath cells (BSCs) layer a presumed control point for radial transport of water and solutes between the vasculature and the leaf mesophyll cells (MCs) is still largely understudied. Using isolated protoplasts, we found that 45% of the 90 genes differentially expressed in BSCs vs. MCs are membrane related and 20% are transport related, suggesting unique functionality of membrane transport in the BSCs, supported also by functional assays (electrophysiology and fluorescence imaging).
Differential gene expression and transport functionality in the bundle sheath versus mesophyll - a potential role in leaf mineral homeostasis.
Specimen part
View SamplesCommonalities and dissimilarities between the IGF1R and INSR pathways
Systems Analysis of Insulin and IGF1 Receptors Networks in Breast Cancer Cells Identifies Commonalities and Divergences in Expression Patterns.
Cell line
View SamplesIdentification of filamin-A as a target for insulin and IGF1 action.
Genome-Wide Analyses Identify Filamin-A As a Novel Downstream Target for Insulin and IGF1 Action.
Cell line, Treatment
View SamplesWe show that the sensitivity of tsc mutant cells to rapamycin is mediated by TORC1 and can be suppressed by overexpression of the 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling. suppressed by overexpression of the putative 2-oxoglutarate-Fe(II) dependent oxygenase, Isp7. We show that Isp7 is a novel master regulator of amino acids uptake that acts via regulation of gene expression, both upstream and downstream of TOR signaling.
Isp7 is a novel regulator of amino acid uptake in the TOR signaling pathway.
No sample metadata fields
View SamplesMolecular profiling of infiltrating monocyte-derived macrophages versus resident kupffer cells following acute liver injury
Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury.
Specimen part, Disease, Time
View SamplesThe placenta is a nonsupportive microenvironment for cancer cells. We showed that breast cancer cells (BCCL) were eliminated from placental implantation sites. During implantation, the placenta manipulates its surrounding matrix, which may induce BCCL elimination. Here, we explored the effect of placenta-induced ECM manipulations on BCCL. During experiments, BCCL (MCF-7/T47D) were cultured on placenta/BCCL-conditioned ECM (Matrigel used for first trimester placenta/BCCL culture and cleared by NH4OH). After culturing the cells, we analyzed cancer cell phenotype (death, count, aggregation, MMP) and signaling (microarray analysis and pathway validation). We found that the BCCL did not attach to previous placental implantation sites and instead, similarly to anoikis-resistant cells, migrated away, displayed increased MMP levels/activity, and formed aggregates in distant areas. T47D were less affected than the MCF-7 cells, since MCF-7 also showed modest increases in cell death, EMT, and increased proliferation. Microarray analysis of the MCF-7 highlighted changes in the integrin, estrogen, EGFR, and TGFb pathways. Indeed, placental ECM reduced ERa, induced Smad3/JNK phosphorylation and increased integrin-a5 expression (RGD-dependent integrin) in the BCCL. Addition of RGD or TGFbR/JNK inhibitors reversed the phenotypic changes. This study helps explain the absence of metastases to the placenta and why advanced cancer is found in pregnancy, and provides possible therapeutic targets for anoikis-resistant cells.
First trimester human placenta prevents breast cancer cell attachment to the matrix: The role of extracellular matrix.
Specimen part, Treatment
View SamplesNovel taste memories, critical for animal survival, are consolidated to form long term memories which are dependent on translation regulation in the gustatory cortex
Fluid consumption and taste novelty determines transcription temporal dynamics in the gustatory cortex.
Sex, Age, Specimen part, Treatment, Time
View Samples