Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The platelet-derived growth factor (PDGF) family consists of three different dimeric forms, AA, BB, and AB, of the two constituent polypeptide chains, A and B. These interact with two different cell surface receptors that, in part, mediate different cellular functions. The various forms of PDGF, as well as the receptors, are expressed at high frequency in glioblastoma multiforme, and it has been suggested that the growth of this tumor might be affected by autocrine loops involving PDGF and its receptors. The present paper focuses on recent discoveries regarding the family of PDGF ligands and receptors, as well as reviews results concerning PDGF-dependent autocrine growth in experimental and spontaneous glioblastoma.
Mol Chem Neuropathol 1989 Feb
PMID:Structural and functional aspects of platelet-derived growth factor and its role in the pathogenesis of glioblastoma. 254 95

Studies were conducted to assess the role of catecholestrogens on ovarian follicular growth using cultured porcine granulosa cells. Effects of the catecholestrogens, 2-hydroxyestradiol (2-OH-E2) and 2-methoxyestradiol (2-MeO-E2) were compared to those of estradiol (E2). Treatment with saturating concentrations of 2-OH-E2 caused a significantly greater decrease in cell numbers measured after 2 days of treatment than E2 treatment. The inhibitory effect of 2-OH-E2 was time and concentration dependent, not associated with a change in the viability of cells, and was partially reversible. The potency of 2-MeO-E2 to inhibit cell numbers was similar to or greater than that of 2-OH-E2. 2-MeO-E2 had a greater inhibitory effect on DNA synthesis, as measured by [3H]thymidine incorporation into trichloroacetic acid-precipitable macromolecules, than 2-OH-E2 or E2 in the absence or presence of insulin, epidermal growth factor or platelet-derived growth factor. Concurrent treatment with epinephrine significantly enhanced the inhibitory effect of 2-OH-E2 on granulosa cell DNA synthesis. Collectively, these studies indicate that catecholestrogens are more potent inhibitors of granulosa cell replication than E2 and 5 alpha-dihydrotestosterone (DHT), and that catecholamines may modulate the antimitotic activity of 2-OH-E2. These results support the hypothesis that catecholestrogens play a role in proliferation of granulosa cells during growth of ovarian follicles.
Mol Cell Endocrinol 1989 Jun
PMID:Catecholestrogens inhibit proliferation and DNA synthesis of porcine granulosa cells in vitro: comparison with estradiol, 5 alpha-dihydrotestosterone, gonadotropins and catecholamines. 254 74

Two tumor cell lines, WM 266-4 melanoma and SW 707 colorectal carcinoma, both of which synthesize platelet-derived growth factor (PDGF) but do not express cell surface PDGF receptor, were tested for the presence of intracytoplasmic PDGF receptor. Using a novel method of intracytoplasmic (newly synthesized), receptor precipitation by the growth factor, we identified a 125,000 molecular weight protein crosslinked with 125I-labeled PDGF in a 140,000 molecular weight complex. In vitro translation of the corresponding mRNA revealed a 125,000 molecular weight product which presumably represents the A-type PDGF receptor. Exogenous PDGF was found to activate synthesis of RNA and cell proliferation.
Exp Mol Pathol 1989 Oct
PMID:Expression of A-type PDGF receptor in cytoplasm of tumor cell lines synthesizing PDGF. 255 73

We have used differentiated L6 myocytes to investigate the regulation of glucose transporter gene expression by insulin and insulin-like growth factor-1 (IGF-1). Chronic exposure to insulin (1 microM) or IGF-1 (10 nm) resulted in a 2- to 5-fold stimulation of 3H-2-deoxy-D-glucose uptake and a corresponding increase in the expression of rat brain/HepG2-type glucose transporter mRNA (GTmRNA) and immunoreactive transporter protein. The dose responses to both insulin and IGF-1 for stimulation of glucose uptake were paralleled by the expression of GTmRNA. Glucose uptake and GTmRNA levels were half maximally stimulated by 350 and 100 nM insulin, respectively, or by 2 nM IGF-1. Comparison of receptor occupancy with stimulation of glucose uptake and GTmRNA expression suggests that insulin exerts its effects through the IGF-1 receptor. Fibroblast growth factor, epidermal growth factor, platelet-derived growth factor, and phorbol ester had little or no effect on GTmRNA expression. These results demonstrate that the IGF-1 receptor mediates chronic regulation of transporter mRNA expression and protein synthesis and activity in cultured rat muscle cells.
Mol Endocrinol 1989 Dec
PMID:Chronic stimulation of glucose transporter gene expression in L6 myocytes mediated via the insulin-like growth factor-1 receptor. 256 Aug 11

The beta 2-adrenergic receptor (ADRB2R) mediates the response of various cel types to neurotransmitters, hormones, and drugs. The platelet-derived growth factor (PDGF) interacts with its receptor (PDGFR) to stimulate mesenchymal cell proliferation. In the human, ADRB2R and PDGFR have been mapped to the q31--q32 region of chromosome 5 (HSA5). Here we report the mapping of Pdgfr and Adrb2r to mouse chromosome 18 (MMU18) using somatic cell hybrid mapping techniques. Together with previous mapping of genes for the glucocorticoid receptor (human locus GRL; mouse locus Gr1-1), the class II HLA invariant chain (human locus PHLAG; mouse locus Ii) and the FMS protooncogene to HSA5 and MMU18, the assignment of both Pdgfr and Adrb2r to MMU18 expands the conserved autosomal syntenic group.
Somat Cell Mol Genet 1989 Jul
PMID:Genes for beta 2-adrenergic receptor and platelet-derived growth factor receptor map to mouse chromosome 18. 256 67

Phorbol esters bind to and activate a family of Protein Kinase C (PKC) proteins, although the degree to which the various PKC forms mediate specific biological functions is unknown. We and others have previously shown that, after exposure to phorbol esters, cultured fibroblasts exhibit increased expression of the mRNA encoding the HepG2/brain glucose transporter (GT mRNA). We therefore studied phorbol ester regulation of GT mRNA in rat fibroblasts which do (R6-PKC3) or do not (R6-C1) stably overproduce a full-length cDNA encoding the PKC beta 1 isotype. When PKC beta 1 is overproduced in a cell that normally has undetectable levels, it is capable of increasing HepG2/brain GT mRNA in response to alpha-D-glucose phorbol 12-myristate 13-acetate (TPA). The level of GT mRNA is maximally induced 6 to 8-fold over basal levels 6 h after exposure to TPA (10 ng/ml) in R6-PKC3 cells that overproduce PKC beta 1, but only 2-fold over basal levels in the control R6-C1 cells. This TPA induced increase in the level of GT mRNA was observed as early as 1 h, peaked by 6-8 h and decreased markedly by 24 h in both cell types. The effect of PKC beta 1 on GT mRNA expression is probably mediated through enhancement of transcription, since the stability of GT mRNA was only minimally affected by TPA. Unlike the enhancement of TPA induced GT mRNA expression caused by overexpression of PKC beta 1, the responses of GT mRNA to calf serum, platelet-derived growth factor, epidermal growth factor, insulin or insulin-like growth factor-1 were the same in both cell types. After pretreatment with 1000 ng/ml TPA in 0.5% calf serum for 24 h, PKC activity was down-regulated and both R6-C1 and R6-PKC3 cells showed complete down-regulation of the GT mRNA responses to an additional treatment with 1000 ng/ml TPA. In contrast to the marked loss of responsiveness to TPA and PKC down-regulation, the responses of GT mRNA to serum, PDGF, EGF, insulin and IGF-1 were unaffected by down-regulation. Thus, our results provide direct evidence for both PKC-dependent and independent pathways regulating GT gene expression. Furthermore, it appears that the level of PKC beta 1 production, rather than down-stream signal transduction events, is the rate-limiting step in the pathway by which TPA induces an increase in GT mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Endocrinol 1989 Dec
PMID:Overproduction of the beta 1 form of protein kinase C enhances phorbol ester induction of glucose transporter mRNA. 262 36

Human platelet-derived growth factor (PDGF) is composed of two polypeptide chains, PDGF-1 and PDGF-2, the human homolog of the v-sis oncogene. Deregulation of PDGF-2 expression can confer a growth advantage to cells possessing the cognate receptor and, thus, may contribute to the malignant phenotype. We investigated the regulation of PDGF-2 mRNA expression during megakaryocytic differentiation of K562 cells. Induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) led to a greater than 200-fold increase in PDGF-2 transcript levels in these cells. Induction was dependent on protein synthesis and was not enhanced by cycloheximide exposure. In our initial investigation of the PDGF-2 promoter, a minimal promoter region, which included sequences extending only 42 base pairs upstream of the TATA signal, was found to be as efficient as 4 kilobase pairs upstream of the TATA signal in driving expression of a reporter gene in uninduced K562 cells. We also functionally identified different regulatory sequence elements of the PDGF-2 promoter in TPA-induced K562 cells. One region acted as a transcriptional silencer, while another region was necessary for maximal activity of the promoter in megakaryoblasts. This region was shown to bind nuclear factors and was the target for trans-activation in normal and tumor cells. In one tumor cell line, which expressed high PDGF-2 mRNA levels, the presence of the positive regulatory region resulted in a 30-fold increase in promoter activity. However, the ability of the minimal PDGF-2 promoter to drive reporter gene expression in uninduced K562 cells and normal fibroblasts, which contained no detectable PDGF-2 transcripts, implies the existence of other negative control mechanisms beyond the regulation of promoter activity.
Mol Cell Biol 1989 Feb
PMID:Functional identification of regulatory elements within the promoter region of platelet-derived growth factor 2. 265 98

The oncogenic retroviruses can be divided into two main categories: those that induce neoplasia after a long latent period (chronic leukemia viruses) and those that induce neoplasia relatively rapidly (acute transforming viruses). Chronic leukemia viruses do not transform cells in tissue culture and contain only the virally encoded genes. By nucleotide sequence comparison, it was possible to show that all retroviruses have a common evolutionary origin. In contrast, acute transforming viruses have substituted viral genes with genetic information specifically implicated in the oncogenic process. These genetic elements (oncogenes) were derived from uninfected host genomes. It was shown that one of the oncogenes, c-sis proto-oncogene, is the structural gene for the B-chain polypeptide of platelet-derived growth factor (PDGF). Furthermore, high level expression of human c-sis resulted in transformation of recipient cells. Similar results have been subsequently obtained for other growth factors, including granulocyte-macrophage colony stimulating factor, transforming growth factor alpha, epidermal growth factor, and basic fibroblast growth factor. It is possible that growth factor gene activation represents one of the steps leading toward malignancy in vivo.
Mol Chem Neuropathol 1989 Feb
PMID:Growth factor genes as oncogenes. 266 Aug 38

We have previously reported that the potent tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) and a factor from fetal calf serum (FCS) markedly enhance the transformation of mouse C3H 10T1/2 and Rat 6 fibroblasts, when added to cultures following transfection with plasmid pT24 DNA that contains an activated c-Ha-ras oncogene. In the present study, we examined possible enhancing or inhibiting effects of various chemicals on the transformation of Rat 6 fibroblasts by T24 DNA when tested in the presence of calf serum, calf serum plus TPA or FCS. We found that, like TPA, the chemicals mezerein, 1-oleoyl-2-acetylglycerol, and phospholipase C increased the yield of T24-induced foci, thus further implicating protein kinase C as a critical constituent in this process. Low concentrations (10(-6)-10(-7)M) of retinoic acid (both trans and 13-cis) also stimulated cell transformation. Several compounds inhibited T24-induced transformation. These included nontoxic concentrations of the calcium ionophore A23187, indomethacin, and epsilon-amino-n-caproic acid. Compounds that failed to exert a significant reproducible effect included vasopressin, vitamin D3, selenium, antipain, Bowman-Birk inhibitor, vitamin B12, epidermal growth factor, platelet-derived growth factor, insulin, and transferrin. These findings suggest that this simple in vitro system might be useful for detecting enhancers and inhibitors of ras oncogene-induced cell transformation and also elucidating their mechanisms of action.
Mol Carcinog 1989
PMID:Effects of various chemical agents on the transformation of rat fibroblasts by an activated c-Ha-ras oncogene. 266 19

Vascular smooth muscle cell (SMC) growth is under the influence of various growth factors. We demonstrate that platelet-derived growth factor (PDGF) stimulates DNA synthesis of cultured bovine aortic SMCs by 2.5- to 3.5-fold. PDGF also exhibits additivity with insulin and insulin-like growth factor I (IGF-I) for DNA synthesis and cellular proliferation. Insulin (2 x 10(-6) M), IGF-I (1 x 10(-8) M), and PDGF (1 x 10(-9) M) cause a 60-80% increase in cell numbers over basal, but PDGF with insulin or IGF causes a 40-150% increase over basal. No additivity between insulin and IGF-I is evident. PDGF also induces commitment to DNA synthesis earlier than insulin or IGF-I. After exposure to PDGF for 4 h, SMCs incorporate 3H-thymidine to 60% of maximum (with PDGF alone) levels (achieved after exposure of 12 h or longer). Insulin and IGF-I exposure for 4 h, on the other hand, achieves 3H-thymidine incorporation that is only a 20-30% of maximum (with insulin or IGF-I alone). Insulin, IGF-I, and PDGF increase mRNA levels of the protooncogene c-myc. This induction begins within 30 min of exposure to these growth factors which causes a 4- to 6-fold increase in c-myc mRNA levels. Additivity is also observed between PDGF with insulin or IGF-I, but not between insulin or IGF-I, in c-myc induction. C-myc mRNA levels remain elevated as long as the hormones are present, although there's a tendency for the mRNA levels to fall off with insulin and IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Aug
PMID:Insulin, insulin-like growth factor I and platelet-derived growth factor interact additively in the induction of the protooncogene c-myc and cellular proliferation in cultured bovine aortic smooth muscle cells. 267 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>