Project description:TGF-β signaling and its induced EMT (Epithelial to mesenchymal transition) play fundamental roles in development and disease including cancers. Although, TGF-β-regulated genes have been extensively studied, with RNA-sequencing (RNA-seq) analysis, new TGF-β-regulated genes are still been identified. Moreover, many significantly regulated genes by TGF-β are not emphasized. This study employs RNA-seq on MCF10A cells treated by TGF-β for 1.5 (this GEO), 24, 48, and 72 (GSE74377) hours and aims to identify novel TGF-β-regulated genes. With 1.5 fold gene expression change (log2 0.58) and p<0.05 at any length of the treatment, 1166 and 861 genes were found to be upregulated and downregulated by TGF-β, respectively. These genes were analyzed for their enrichments in KEGG pathways and prognostic markers of cancers. Several genes of interest were further analyzed for their regulation by TGF-β across cell lines and their functions in context of TGF-β were further studied. This study systematically analyzed TGF-β-regulated genes and revealed novel factors mediating the pro-migratory role of TGF-β signaling, hence, sheds a light on the understanding of the mechanisms underlying the role of TGF-β signaling in cancer development.
Project description:TGF-betas have complex roles in tumorigenesis, with context-dependent effects that can either suppress or promote tumor progression. Our goal was to use integrated genomic approaches in a model of human breast cancer progression to identify core TGF-beta-regulated genes that specifically reflect the tumor suppressor activity of TGF-beta. The model consisted of the non-tumorigenic MCF10A (“M1”), the premalignant MCF10AT1k.cl2 (“M2”), the early malignant MCF10Ca1h (“M3”) and the highly malignant, metastatic MCF10Ca1a.cl1 (“M4”) cell lines. We have previously shown that tumor suppressor activity of TGF-beta is lost in the highly malignant M4 cells. To determine how the spectrum of TGF-beta-regulated genes changes with cancer progression, we performed gene expression array analysis on four cell lines of the MCF10A-based model of breast cancer progression (M1-M4) cultured in vitro under serum-free conditions and treated with TGF-beta (5ng/ml plus condition) or vehicle (minus condition) for 1h or 6h.
Project description:Bovine articular chondrocytes were grown in micromass culture and were either untreated or treated with 5 ng TGF-b1/ml for 8 hours to identify genes regulated by TGF-b.
Project description:Bovine articular chondrocytes were grown in micromass culture and were either untreated or treated with 5 ng TGF-b1/ml for 8 hours to identify genes regulated by TGF-b. Six total samples were analyzed. Three biological replicates of untreated bovine articular chondrocytes grown in micromass culture and three biological replicates of bovine articular chondrocytes grown in micromass culture and treated with 5ng TGF-b1/ ml for 8 hours.
Project description:Recent studies demonstrate that Ca2+ signaling has an important role in EMT. Use of Ca2+ blockers such as 2APB can inhibit cell migration induced by TGF-β. Interestingly, we see an unexpected increase in Snail expression upon Ca2+ blocker treatment of both MCF10A and NMuMG cells; this increase is not observed with 2APB treatment alone. Therefore, we believe that 2APB plays a synergistic role with TGF-β in Snail induction. We propose to investigate the gene networks that change following 2APB +TGF-β treatment.
Project description:To identify TGF-β regulated lncRNAs in glioblastoma, we performed a genome-wide microarray screen in T98G glioma cells. T98G cells were treated with 10 ng/ml TGF-β (24h) and differentially expressed lncRNAs were identified using microarray in comparison with control cells.
Project description:TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. The effect of TGF-beta on the regulation of gene expression is cell-type specific. In order to identify TGF-beta regulated genes in different cell-types, we followed the expression profiling approach. Keywords: cell type specific response to TGF-beta
Project description:Long non-coding RNAs (lncRNAs) are emerging as pivotal modulators of signaling trnasduction, and thereby regulate multiple pathological processes including cancer. TGF-beta signaling contributes to cancer metastasis by inducing epithelial-to-mesenchymal transition (EMT). To screen lncRNAs that are induced by TGF-beta, MCF10A-M1, MCF10A-M2 and MDA-MB-231 cells were stimulated with TGF-beta (5 ng/mL) fo 0 h, 2 h, 8 h and 24 h. RNA was extracted from those cells and analyzed by RNA-seq.