scholarly journals Myc Is an Essential Negative Regulator of Platelet-Derived Growth Factor Beta Receptor Expression

2000 ◽  
Vol 20 (18) ◽  
pp. 6768-6778 ◽  
Author(s):  
Sara K. Oster ◽  
Wilson W. Marhin ◽  
Charlotte Asker ◽  
Linda M. Facchini ◽  
Patrick A. Dion ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Cell Types ◽  
Receptor Expression ◽  
Negative Regulator ◽  
Platelet Derived Growth Factor ◽  
Mrna Levels ◽  
Proliferating Cells ◽  
Receptor Complexes ◽  
Β Receptor

ABSTRACT Platelet-derived growth factor BB (PDGF BB) is a potent mitogen for fibroblasts as well as many other cell types. Interaction of PDGF BB with the PDGF β receptor (PDGF-βR) activates numerous signaling pathways and leads to a decrease in receptor expression on the cell surface. PDGF-βR downregulation is effected at two levels, the immediate internalization of ligand-receptor complexes and the reduction in pdgf-βr mRNA expression. Our studies show that pdgf-βr mRNA suppression is regulated by the c-myc proto-oncogene. Both constitutive and inducible ectopic Myc protein can suppress pdgf-βr mRNA and protein. Suppression of pdgf-βr mRNA in response to Myc is specific, since expression of the related receptorpdgf-αr is not affected. We further show that Myc suppresses pdgf-βr mRNA expression by a mechanism which is distinguishable from Myc autosuppression. Analysis of c-Myc-null fibroblasts demonstrates that Myc is required for the repression of pdgf-βr mRNA expression in quiescent fibroblasts following mitogen stimulation. In addition, it is evident that the Myc-mediated repression of pdgf-βr mRNA levels plays an important role in the regulation of basalpdgf-βr expression in proliferating cells. Thus, our studies suggest an essential role for Myc in a negative-feedback loop regulating the expression of the PDGF-βR.

scholarly journals Prognostic Significance of Stromal Platelet-Derived Growth Factor β-Receptor Expression in Human Breast Cancer

2009 ◽  
Vol 175 (1) ◽  
pp. 334-341 ◽  
Author(s):  
Janna Paulsson ◽  
Tobias Sjöblom ◽  
Patrick Micke ◽  
Fredrik Pontén ◽  
Göran Landberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Human Breast Cancer ◽  
Prognostic Significance ◽  
Receptor Expression ◽  
Platelet Derived Growth Factor ◽  
Human Breast ◽  
Β Receptor

scholarly journals Repression of platelet-derived growth factor beta-receptor expression by mitogenic growth factors and transforming oncogenes in murine 3T3 fibroblasts.

1995 ◽  
Vol 15 (3) ◽  
pp. 1244-1253 ◽  
Author(s):  
C Vaziri ◽  
D V Faller
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Surface ◽  
Growth Arrest ◽  
Serum Deprivation ◽  
Receptor Expression ◽  
Platelet Derived Growth Factor ◽  
Mrna Levels ◽  
Beta Receptor ◽  
3T3 Fibroblasts

Platelet-derived growth factor BB (PDGF-BB) is an important extracellular factor for regulating the G0-S phase transition of murine BALB/c-3T3 fibroblasts. We have investigated the expression of the PDGF beta receptor (PDGF beta R) in these cells. We show that the state of growth arrest in G0, resulting from serum deprivation, is associated with increased expression of the PDGF beta R. When the growth-arrested fibroblasts are stimulated to reenter the cell cycle by the mitogenic action of serum or certain specific combinations of growth factors, PDGF beta R mRNA levels and cell surface PDGF-BB-binding sites are markedly downregualted. Oncogene-transformed 3T3 cell lines, which fail to undergo growth arrest following prolonged serum deprivation, express constitutively low levels of the PDGF beta R mRNA and possess greatly reduced numbers of cell surface PDGF receptors, as determined by PDGF-BB binding and Western blotting (immunoblotting). Nuclear runoff assays indicate the mechanism of repression of PDGF beta R expression to be, at least in large part, transcriptional. These data indicate that expression of the PDGF beta R is regulated in a growth state-dependent manner in fibroblasts and suggest that this may provide a means by which cells can modulate their responsiveness to the actions of PDGF.

Activation of 5-HT7 receptors increases neuronal platelet-derived growth factor β receptor expression

2012 ◽  
Vol 511 (2) ◽  
pp. 65-69 ◽  
Author(s):  
Maryam S. Vasefi ◽  
Jeff S. Kruk ◽  
Hui Liu ◽  
John J. Heikkila ◽  
Michael A. Beazely
Keyword(s):  
Growth Factor ◽  
Receptor Expression ◽  
Platelet Derived Growth Factor ◽  
Β Receptor

Inducible platelet-derived growth factor D-chain expression by angiotensin II and hydrogen peroxide involves transcriptional regulation by Ets-1 and Sp1

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2322-2329 ◽  
Author(s):  
Mary Yanxia Liu ◽  
Melanie Eyries ◽  
Chunyan Zhang ◽  
Fernando S. Santiago ◽  
Levon M. Khachigian
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Transcriptional Start Site ◽  
Cell Types ◽  
Platelet Derived Growth Factor ◽  
Dna Binding Domain ◽  
Start Site ◽  
Extension Analysis

AbstractPlatelet-derived growth factor D-chain (PDGF-D) is the newest member of the PDGF family of mitogens and chemoattractants expressed in a wide variety of cell types, including vascular smooth muscle cells (SMCs). The molecular mechanisms regulating PDGF-D transcription are not known. Primer extension analysis mapped a single transcriptional start site to the ccAGCGC motif with several potential Ets motifs located upstream. Ets-1, but not Ets-1 bearing only the DNA-binding domain, activates the PDGF-D promoter and mRNA expression in SMCs. Ets site D3 (–470GGAT–467) is singly required for basal and Ets-1–inducible PDGF-D promoter-dependent expression. D3 supports the interaction of endogenous and recombinant Ets-1 and Sp1. Sp1, like Ets-1, induces PDGF-D transcription and mRNA expression, which is blocked by mutant Ets-1. H2O2 stimulates Ets-1, but not Sp1, and activates D3-dependent PDGF-D transcription. Ets-1 and Sp1 siRNA block peroxide-inducible PDGF-D expression. Angiotensin II (ATII) induction of PDGF-D and Ets-1 was blocked by prior incubation of the cells with PEG-catalase, but not BSA, indicating that ATII-inducible Ets-1 and PDGF-D expression is mediated via H2O2. Thus, 2 separate trans-acting factors regulate PDGF-D transcription, alone and in response to oxidative stress.

scholarly journals Differential modulation of degradative and repair responses of interleukin-1-treated chondrocytes by platelet-derived growth factor

1993 ◽  
Vol 292 (1) ◽  
pp. 129-136 ◽  
Author(s):  
A K Harvey ◽  
S T Stack ◽  
S Chandrasekhar
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Articular Chondrocytes ◽  
Interleukin 1 ◽  
Receptor Expression ◽  
Platelet Derived Growth Factor ◽  
Proteinase Activity ◽  
Proteoglycan Synthesis ◽  
Mrna Levels ◽  
The Matrix

Interleukin 1 (IL-1) plays a dual role in cartilage matrix degeneration by promoting extracellular proteinase action such as the matrix metalloproteinases (increased degradation) and by suppressing the synthesis of extracellular matrix molecules (inhibition of repair). Platelet-derived growth factor (PDGF) is a wound-healing hormone which is released along with IL-1 during the inflammatory response. Since previous studies have shown that PDGF enhances IL-1 alpha effects on metalloproteinase activity, in this report, we have examined whether PDGF modifies IL-1 beta effects on cartilage proteoglycan synthesis. Initially, we confirmed that rabbit articular chondrocytes treated with IL-1 beta + PDGF induced higher proteinase activity, in comparison with IL-1-treated cells. We further observed that the increased proteinase activity correlated with an increase in the synthesis of collagenase/stromelysin proteins and a corresponding increase in the steady-state mRNA levels for both the enzymes. Studies on IL-1 receptor expression suggested that PDGF caused an increase in IL-1 receptor expression which, by augmenting the IL-1 response, may have led to the increase in proteinase induction. Analysis of proteoglycan synthesis confirmed that IL-1 reduced the incorporation of sulphated proteoglycan, aggrecan, into the extracellular matrix of chondrocytes, whereas PDGF stimulated it. However, cells treated with IL-1 + PDGF synthesized normal levels of aggrecan. This is in contrast with cells treated with IL-1 + fibroblast growth factor, in which case only proteinase activity was potentiated. The results allow us to conclude that (a) the two effector functions that play a role in matrix remodelling, namely matrix lysis (proteinase induction) and matrix repair (proteoglycan synthesis), occur via distinct pathways and (b) PDGF may play a crucial role in cartilage repair by initially causing matrix degradation followed by promoting new matrix synthesis.

Activated Platelet-Derived Growth Factor β Receptor Expression, P13K-AKT Pathway Molecular Analysis, and Transforming Signals in Equine Sarcoids

2009 ◽  
Vol 46 (4) ◽  
pp. 589-597 ◽  
Author(s):  
G. Borzacchiello ◽  
S. Mogavero ◽  
G. De Vita ◽  
S. Roperto ◽  
L. Della Salda ◽  
...  
Keyword(s):  
Growth Factor ◽  
Normal Skin ◽  
Receptor Expression ◽  
Cyclin D3 ◽  
Platelet Derived Growth Factor ◽  
Regulatory Subunit ◽  
In Vivo Model ◽  
Physical Interaction ◽  
Equine Sarcoid ◽  
Β Receptor

The equine sarcoid is the most common dermatologic neoplasm reported in horses. Bovine papillomavirus (BPV) types 1 and 2 are associated with sarcoids, in which the expression of the major transforming oncoprotein (E5) is often recorded. The transformation activity of the virus is due to the binding of the E5 to the platelet-derived growth factor β receptor (PDGFβ-r). In the present study, we show by Western blot in 4 sarcoid samples and 3 normal equine skin samples that the PDGFβ-r is more phosphorylated in sarcoid tissue than in normal skin ( P < .001). Furthermore, the physical interaction between the activated receptor and the 85-kDa regulatory subunit (p85) of phosphatidylinositol-3-kinase (PI3K) is shown by coimmunoprecipitation. The PI3K-AKT-cyclin D3 molecular pathway downstream to the activation of the PDGFβ-r is shown to be expressed, and the amount of the investigated molecules is higher than normal ( P < .001), suggesting an activation of these effectors in sarcoids. Further, we demonstrate that phospho-JNK and phospho-JUN are more expressed in sarcoids than in normal skin. Our results provide new insights into the pathogenesis of equine sarcoids and support the validity of this in-vivo model to further characterize the molecular pathways underlying BPV E5-induced carcinogenesis.

miR-126 regulates platelet-derived growth factor receptor-α expression and migration of primary human osteoblasts

2015 ◽  
Vol 396 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Yvonne Schmidt ◽  
Filip Simunovic ◽  
Sandra Strassburg ◽  
Dietmar Pfeifer ◽  
G. Björn Stark ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Development ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Negative Regulator ◽  
Platelet Derived Growth Factor ◽  
Loss Of Function ◽  
Human Osteoblasts ◽  
Primary Human Osteoblasts ◽  
And Migration

Abstract Adequate vascularization is an essential requirement for bone development, fracture healing and bone tissue engineering. We have previously described the coculture of primary human osteoblasts (hOBs) and human endothelial cells (HUVECs), designed to investigate the interactions between these cells. In this system, we showed that cocultivation of these two cell types leads to a downregulation of platelet-derived growth factor receptor-α (PDGFR-α) in hOBs, which was a consequence of reduced mRNA stability. In the current study we investigated the possible involvement of microRNAs in this process. Firstly, we performed a microarray analysis of osteoblastic miRNAs following cocultivation with HUVECs, revealing an upregulation of miR-126. This result was confirmed by RT-qPCR, and we observed that the increase is dependent on direct cell-to-cell contacts. Gain-of-function and loss-of-function experiments showed that miR-126 is a negative regulator of PDGFR-α mRNA. Additionally, migration of hOBs was inhibited by miR-126 overexpression and stimulated by miR-126 inhibition. Addition of PDGFR-α blocking antibody to hOB culture also inhibited hOB migration. There was no effect of miR-126 modulation on osteoblast proliferation, apoptosis rate or differentiation. In conclusion, we report that the miR-126/PDGFR-α system regulates the migratory behavior of human osteoblasts, without exerting effects on cell survival and differentiation.

Sign in / Sign up

Export Citation Format

Share Document