Gene-expression profiles of BMP signaling-affected SK-OV-3 cells
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ABSTRACT: Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor beta (TGF-β) superfamily. By regulating target gene transcription, BMPs control various cellular processes, such as proliferation, differentiation, apoptosis and migration. In addition, rBMP2 was used to observe BMP signaling in treatment of ovarian cancer cell line SK-OV-3. We attempted to address the possible roles of BMP signaling by inhibiting a wide-range of downstream pathways using a small molecule inhibitor of type I BMPRs, dorsomorphin. The potential utility of this molecule as a molecular inhibitor of BMP signaling in treatment of ovarian cancer cell line SK-OV-3 was also evaluated. SK-OV-3 cells were incubated in 12 separate culture dishes, 3 dishes with PBS, 3 dishes with recombinant BMP2 (rBMP2) (100 ng/ml), 3 dishes with DM (5 μM) and 3 dishes with recombinant BMP2 (rBMP2) (100 ng/ml) plus DM (5 μM) in the culture medium for 24 hours prior to the analysis.
Project description:Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor beta (TGF-β) superfamily. By regulating target gene transcription, BMPs control various cellular processes, such as proliferation, differentiation, apoptosis and migration. In addition, rBMP2 was used to observe BMP signaling in treatment of ovarian cancer cell line SK-OV-3. We attempted to address the possible roles of BMP signaling by inhibiting a wide-range of downstream pathways using a small molecule inhibitor of type I BMPRs, dorsomorphin. The potential utility of this molecule as a molecular inhibitor of BMP signaling in treatment of ovarian cancer cell line SK-OV-3 was also evaluated.
Project description:Bone morphogenetic proteins (BMPs) regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation. We used cDNA microarrays to elucidate regulators of BMP-2-induced osteoblast differentiation.
Project description:Both bone morphogenetic proteins (BMPs) and histone deacetylases (HDACs) have previously been established to play a role in the development of the three major cell types of the central nervous system: neurons, astrocytes, and oligodendrocytes. We have previously established a connection between these two protein families, showing that HDACs suppress BMP-promoted astrogliogenesis in the embryonic striatum. Since HDACs act in the nucleus to effect changes in transcription, an unbiased analysis of their transcriptional targets could shed light on their downstream effects on BMP-signaling. Using neurospheres from the embryonic striatum as an in vitro system to analyze this phenomenon, we have performed microarray expression profiling on BMP2- and trichostatin A (TSA)-treated cultures, followed by validation of the findings with quantitative RT-PCR and protein analysis. Neurospheres from the embryonic striatum were used to analyze cellular differentiation into neurons and astrocytes in vitro. To analyze the role of BMP2 and the HDAC-inhibitor TSA in this system, neurospheres were treated with TSA or BMP2 for 24 h, and mRNA was extracted after 6 and 24 h of the respective treatment.
Project description:Bone morphogenetic proteins (BMPs) regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation, while it inhibits myogenic differentiation in C2C12 cells. We used cDNA microarrays to elucidate regulators of BMP-2-induced osteoblast differentiation.
Project description:The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip and stalk cells. However, the crosstalk of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 and Notch signaling, and act via TAZ-Hippo signaling pathway. BMPs were found to be regulated after VEGF gene transfer in C57/Bl6 mice and in a porcine myocardial ischemia model. BMPs 2/4/6 were identified as endothelium-specific targets of VEGF. BMP2 modulated VEGF-mediated endothelial sprouting via Delta like Canonical Notch Ligand 4 (DLL4). BMP6 modulated VEGF signaling by regulating VEGFR2 expression and acted via Hippo signaling effector TAZ, known to regulate cell survival/proliferation, and to be dysregulated in cancer. In a matrigel plug assay in nude mice BMP6 was further demonstrated to induce angiogenesis. BMP6 is the first member of BMP family found to directly regulate both Hippo signaling and neovessel formation. It may thus serve as a target in pro/anti-angiogenic therapies.
Project description:XEN cells are derived from the primitive endoderm of mouse blastocysts. In culture and in chimeras they exhibit properties of parietal endoderm. However, BMP signaling promotes XEN cells to form an epithelium and differentiate into visceral endoderm (VE). Of the several different subtypes of VE described, BMP induces a subtype that is most similar to the VE adjacent to the trophoblast-derived extraembryonic ectoderm. The experiment was performed to gain insight into genes regulated by BMP and activin in XEN cells, and also to more precisely define the VE subtypes formed in culture. IM8A1 XEN cells were treated for 6 days with BMP2 (20 ng/ml, R&D Systems), activin A (30 ng/ml, Peprotech), both, or neither in GMEM + 10% fetal bovine serum.
Project description:Human pulmonary arterial endothelial cells (PAECs) and blood outgrowth endothelial cells (BOECs) from healthy subjects were stimulated with BMP9, BMP2 or BMP6. and assessed for changes in gene transcription by microarray. Unlike BMP2 and BMP6, which had negligible impacts on gene expression, BMP9 induced the differential regulation of 1883 genes (adjusted P value < 0.05), including several key components of canonical BMP signaling such as ID1, ID2 and BMPR2.
Project description:Bone Morphogenetic Proteins (BMPs), a subgroup of the TGF-ï¢ superfamily, were originally isolated from bone on the basis of their ability to induce ectopic bone development. While BMPs are involved in a wide range of developmental and physiological functions, very few vertebrate target genes in this pathway have been identified. To identify target genes regulated by the BMP growth factor family in Xenopus, large-scale microarray analyses were conducted to discover genes directly activated by this factor in dissociated animal cap tissues treated with a combination of the protein synthesis inhibitor cycloheximide and BMP2. Keywords = Xenopus Keywords = BMP Keywords = microarray Keywords = development Keywords = target genes
Project description:Bone morphogenic proteins (BMPs) function in virtually all tissues with cell-type specific outcomes. Since there are a relatively small number of BMP receptors this exquisite signaling specificity requires additional molecules to regulate the output of this pathway. We demonstrated that the receptor tyrosine kinase MuSK that is selectively expressed in muscle and plays a critical role in synapse formation and maintenance binds to BMP4 and related BMPs. Since BMPs regulate the transcription of a set of genes, we performed microarrays for wild-type and MuSK null muscle cells to test if MuSK regulates BMP responses in muscle cells. We shought to determine if MuSK regulates BMP responses in muscle cells and if the cell context made any difference in MuSK regulation of BMP pathway. To test this, expression profiles of untreated vs. BMP4-treated undifferentiated myoblast and differentiated myotube cultures were generated for both wild-type and MuSK-null genotypes. All conditions were done in triplicates. In total 24 arrays were analyzed.