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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using gel-retardation assay we have investigated binding of nuclear proteins to the mouse c-fos promoter region 30 b.p. long (nucleotides (-464) - (-435) from TATA-box), localized upstream of PDGF-dependent induction element. It was found that some factors from nuclear extracts of various human and murine cells bind to this promoter region. After gel-retardation of DNA- protein complexes from nuclear extracts of quiescent and stimulated with 20% fetal calf serum cells we observed only one retarded band, while after gel-retardation of DNA-protein complexes from proliferating pseudonormal and tumorigenic cells we observed the appearance of additional retarded band with higher mobility in PAAG. We also have determined the molecular weights of factors interacting with investigated c-fos promoter region by affinity modification method. The molecular weights of both factors are 59 kDa. The equality of molecular weights of investigated factors suggests that these factors might be different forms of one nuclear protein.
Mol Biol (Mosk)
PMID:[Binding of nuclear proteins with segments of the c-fos gene promotor, localized in position (-465)-(-435) correlates with cell proliferation]. 805 48

Using flow cytometry, thymidine uptake into DNA, and expression of two growth-related genes, histone 3 and c-myc, we found an increase in the proportion of distal lung epithelial cells in the G0/G1 phase of the cell cycle with advancing gestation. Since our previous studies had demonstrated that platelet-derived growth factor (PDGF) is essential for the progression of these cells from the G0/G1 to the S phase of cell cycle, we investigated the gene and protein expression of PDGF-related genes (PDGF-A, PDGF-B, alpha-receptor, and beta-receptor) in distal fetal lung epithelial cells. The cells transcribed all the PDGF-related genes and translated the PDGF-A and PDGF-B mRNAs into protein, as demonstrated by immunocytochemistry and immunoprecipitation. To explore an autocrine role for PDGF in distal fetal lung epithelial cells, intervention studies using PDGF-A and -B chain-specific antisense oligodeoxynucleotides (ODN) were carried out. Antisense PDGF-B ODN, but not antisense PDGF-A ODN, significantly reduced the DNA synthesis of these cells. The inhibitory effect of antisense PDGF-B ODN on DNA synthesis was reversed by the addition of exogenous PDGF-BB, which supports an autocrine role in the DNA synthesis of these cells. We also examined the expression of PDGF genes in distal fetal lung epithelial cells during late gestation. PDGF-A chain and beta-receptor gene expressions declined with advancing gestation, whereas expression of message for PDGF-B chain and alpha-receptor increased. The increases in message for PDGF-B chain and alpha-receptor with advancing gestation were due to a greater rate of transcription, whereas the developmental decrease of PDGF-A chain and beta-receptor mRNAs was caused by a decrease in RNA stability. Taken together with the ODN data, these results suggest that the G0/G1 cell cycle arrest of distal lung epithelial cells during late fetal gestation is due to a decrease in PDGF beta-receptor expression by the cells.
Am J Respir Cell Mol Biol 1994 Sep
PMID:Ontogeny and regulation of platelet-derived growth factor gene expression in distal fetal rat lung epithelial cells. 808 63

The effect of platelet-derived growth factor-BB on adult rat Leydig cell steroidogenesis has been determined using culture conditions which maintain testosterone production and responsiveness to luteinising hormone for 3 days. A significant stimulation of testosterone levels was observed in acute response to a maximally stimulating dose (8 ng/ml) of rat luteinising hormone on the third day of culture, but was dependent on pre-exposure of the Leydig cells to PDGF-BB for 2 days, whilst maintained in the presence of a minimum dose (0.1 ng/ml) of rat luteinising hormone. These data demonstrate a very discrete action of PDGF-BB on adult rat Leydig cell steroidogenesis in vitro, but whether or not this constitutes a significant paracrine effect in vivo remains to be established.
Mol Cell Endocrinol 1993 Nov
PMID:Discrete stimulatory effects of platelet-derived growth factor (PDGF-BB) on Leydig cell steroidogenesis. 814 94

Malignant astrocytoma is the most common primary human brain tumor. Most astrocytomas express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could close an autocrine loop. It is not known whether these autocrine loops contribute to the transformed phenotype of astrocytoma cells or are incidental to that phenotype. Here we show that dominant-negative mutants of the PDGF ligand break the autocrine loop and revert the phenotype of BALB/c 3T3 cells transformed by the PDGF-A or PDGF-B (c-sis) gene. Then, we show that these mutants are selective in that they do not alter the phenotype of 3T3 cells transformed by an activated Ha-ras or v-src gene or by simian virus 40. Finally, we show that these mutants revert the transformed phenotype of two independent human astrocytoma cell lines. They have no effect on the growth of human medulloblastoma, bladder carcinoma, or colon carcinoma cell lines. These observations are consistent with the view that PDGF autocrine loops contribute to the transformed phenotype of at least some human astrocytomas.
Mol Cell Biol 1993 Dec
PMID:Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. 824 42

Uncontrolled cell growth is at the basis of neoplastic proliferation and arteriosclerotic lesions. In vitro proliferation of vascular smooth muscle cells, Balb c/3T3 fibroblasts, retinal neuroepithelial cells and neuroblastoma cells is inhibited by d-alpha-tocopherol. On the contrary Chinese hamster ovary cells, osteosarcoma cells and macrophages are not sensitive. PDGF-BB activated proliferation is highly d-alpha-tocopherol sensitive while lysophosphatidic acid induced growth is poorly inhibited. d-beta-Tocopherol, an analogue of d-alpha-tocopherol, with similar antioxidant properties, does not inhibit proliferation. Protein kinase C activity is inhibited by d-alpha-tocopherol but not by d-beta-tocopherol, suggesting a central role of this enzyme in the control of cell proliferation by d-alpha-tocopherol. Activation of the transcription activation complex AP-1 (but not NFKB) is prevented by d-alpha-tocopherol and not by d-beta-tocopherol.
Mol Aspects Med 1993
PMID:d-alpha-tocopherol control of cell proliferation. 826 42

Evidence of receptor/ligand interactions that regulate testis cell function was sought in order to broaden the current understanding of the molecular basis of testis cell function. Using reverse transcription and the polymerase chain reaction, we have obtained novel evidence for the expression of three mRNAs encoding receptor tyrosine kinases in the adult rat testis: the platelet-derived growth factor type A receptor (PDGF-RA), the basic fibroblast growth factor receptor (flg), and fetal liver kinase 1 (Flk-1). A 6.8 kb transcript encoding the PDGF-RA was observed in RNA prepared from testes of rats aged day 5 through adult, with a decline in relative abundance with increasing age after day 17. Analysis of mRNA from isolated cell preparations (day 21 Sertoli cells, adult Leydig cells, round spermatids, and primary spermatocytes) and testes depleted of specific cell types [ethane dimethane sulfonate (EDS)-treated and cryptorchid] indicated that the Leydig cell was the predominant source of this mRNA in the adult testis. The addition of PDGF-BB to cultures of highly purified adult rat Leydig cell preparations resulted in a 40% increase in LH-stimulated testosterone production, confirming a role for this growth factor in regulation of Leydig cell function. These data indicate that the Leydig cell is a principal site of action of PDGF in the testis.
Mol Reprod Dev 1993 Dec
PMID:Identification of receptor tyrosine kinases in the rat testis. 830 6

A non-receptor-binding mutant of the platelet-derived growth factor (PDGF) A chain, PDGF-0, was generated by exchanging 7 amino acids in the sequence. The mutant chains formed dimers that were similar to wild-type PDGF-AA with regard to stability and rate of processing to the mature 30-kDa secreted forms. Moreover, the mutant chains formed disulfide-bonded heterodimers with the PDGF B chain in NIH 3T3 cells heterodimer underwent the same processing and secretion as PDGF-AB. Transfection of c-sis-expressing 3T3 cells with PDGF-0 significantly inhibited the transformed phenotype of these cells, as determined by the following criteria. (i) Compared with PDGF-0-negative clones, PDGF-0-producing clones showed a reverted morphology. (ii) Clones producing PDGF-0 grew more slowly than PDGF-0-negative clones, with a fivefold difference in cell number after 14 days in culture. (iii) The expression of PDGF-0 completely inhibited the ability of the c-sis-expressing 3T3 cells to form colonies in soft agar; this inhibition was overcome by the addition of recombinant PDGF-BB to the culture medium, showing that the lack of colony formation of these cells was not due to a general unresponsiveness to PDGF. The specific expression of a PDGF-0/PDGF wild-type heterodimer in COS cells revealed that the affinity of the mutant heterodimer for the PDGF alpha receptor was decreased by approximately 50-fold compared with that of PDGF-AA. Thus, we show that a non-receptor-binding PDGF A-chain mutant neutralizes in a trans-dominant manner the autocrine transforming potential of the c-sis/PDGF B chain by forming low-affinity heterodimers with wild-type PDGF chains. This method of specifically antagonizing the effect of PDGF may be useful in investigations of the role of PDGF in normal and pathological conditions.
Mol Cell Biol 1993 Jul
PMID:Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant. 832 Dec 14

Overexpression of platelet-derived growth factor (PDGF)-A as well as PDGF-B chain mRNA has previously been reported in human mesothelioma cell lines. In this report, it has been established that the A but not the B chain protein is expressed at detectable levels in cell lysates and conditioned medium from these cell lines. In order to investigate the effect of overexpression of PDGF-A chain in a human mesothelial cell model system, a retroviral vector containing a human PDGF-A chain cDNA insert under the control of the Moloney murine leukemia virus (MoMLV) promoter was inserted into the SV-40 T-antigen immortalized human mesothelial cell line MeT-5A. Selected cells showed overexpression of PDGF-A chain relative to MeT-5A and induced tumors in athymic nude mice. PDGF-A chain overexpression was also found in the tumor specimens excised from the mice. PDGF-A mRNA and protein were expressed at a higher level in the tumor explant cell lines, suggesting a correlation of tumorigenicity with A chain production.
Am J Respir Cell Mol Biol 1993 Feb
PMID:Tumorigenic conversion of human mesothelial cells as a consequence of platelet-derived growth factor-A chain overexpression. 842 11

Neonatal vascular smooth muscle cells (SMC) in culture have been demonstrated to be quite different from adult SMC and to be similar to intimal SMC in animal models. To characterize human neonatal vascular SMC in culture, cultures of arterial SMC were prepared by an explant method from the subclavian arteries of autopsied patients (10 adults and 6 neonates). The morphology and growth characteristics of these cells were compared. All cells were positively immunostained with HHF 35, a monoclonal antibody specific for muscle actin. Electron microscopically, both adult and neonatal SMC were of synthetic phenotype. SMC from neonates had a short population doubling time (PDT, 28.6 +/- 7.5 hr) and high saturation density (SD, 37.5 +/- 11.9 x 10(4) cells/cm2). They did not show hill and valley growth patterns. Among the SMC cultured from adult media, two subtypes were distinguished, based on their growth characteristics. Classical adult SMC (7 of 10 cases) grew in hill and valley patterns with long PDT and low SD values (61.7 +/- 28.8 hr, 6.5 +/- 1.9 x 10(4) cells/cm2, respectively). The second subtype (3 of 10 cases), neonatal-type adult SMC, had PDT and SD values (22.9 +/- 4.0 hr, 31.3 +/- 14.7 x 10(4) cells/cm2, respectively) similar to those of neonatal SMC. Intimal SMC became senescent in early phases of subculture. To test for the possible participation of autocrine growth factors in the heterogeneity of the growth patterns, Northern blot analysis was conducted for PDGF-A, TGF-beta, c-myc, and c-fos mRNA in three types of SMC. There was no significant difference in these mRNA levels between the SMC. We demonstrated that human neonatal vascular SMC in culture are quite different in their growth characteristics from classical adult SMC in culture and that neonatal-type SMC can be isolated from adult media.
Exp Mol Pathol 1993 Feb
PMID:Human neonatal and adult vascular smooth muscle cells in culture. 845 35

In human renal mesangial cells, platelet derived growth factor (PDGF)-A chain is subject to regulation by protein kinase C (PKC) activator, phorbol ester (phorbol 12-myristate 13-acetate, PMA). Treatment of mesangial cells with PMA increases PDGF-A chain mRNA abundance as analyzed by Northern blot hybridization. In contrast to the effect of PMA, the inactive analog phorbol had no effect on PDGF-A chain mRNA levels, while the PKC inhibitor H7 markedly reduced the PMA-induced increment in PDGF-A chain mRNA. To determine the mechanism by which PMA increases the abundance of this gene, transcription rate was measured by nuclear transcript elongation assay. Treatment of mesangial cells with PMA resulted in a 2-fold increase in PDGF-A chain gene transcription. In addition, we analyzed the effects of PMA on PDGF-A chain mRNA half-life as measured directly by pulse-chase method. PDGF-A chain mRNA has a half-life of about 106 min. The PDGF-A chain mRNA half-life was reduced by 30% (t1/2 = 74 min) when mesangial cells were incubated with PMA. Our results demonstrate that in human renal mesangial cells, the regulation of PDGF-A chain gene expression by PMA is primarily at the level of transcription.
Mol Cell Endocrinol 1993 Feb
PMID:Platelet derived growth factor-A chain gene expression in cultured mesangial cells: regulation by phorbol ester at the level of mRNA abundance, transcription and mRNA stability. 847 49


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