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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This recent study describes the growth characteristics of ACR skin fibroblasts in culture and their differential susceptibility to transformation by Kirsten murine sarcoma virus (Ki-MSV). The SF were derived from normal appearing subepidermoid biopsies of ACR individuals, their progeny and ocntrols. Normal SF were contact-inhibited and grew only in 15% FCS. SF of ACR subjects, and some asymptomatic ACR progeny were not contact inhibited, grew in both 1% and 15% FCS and were considerably more susceptible to transformation by Ki-MSV than were control SF. The virally transformed SF showed a loss of anchorage dependency in methylcellulose and formed tumors in athymic mice. The results suggest the presence of early and previously undetected metabolic lesions in SF from clinically asymptomatic subjects. These phenotype markers are currently evaluated for their utility in the clinical diagnosis of individuals with latent ACR and those at increased risk for colon cancer. SF from ACR individuals have been recently shown to contain significant alterations in the intracellular distribution of actin (R. Pollack and L. Kopelovich, in preparation), and elevated levels of plasminogen activator (L. Kopelovich).
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PMID:Recent studies on the identification of proliferative abnormalities and of oncogenic potential of cutaneous cells in individuals at increased risk of colon cancer. 1 61

This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF). Low concentrations of retinoic acid (RA) (10(-6)-10(-10) M) and the retinoids stimulated PA synthesis in CEF; the maximal stimulation achieved, 9--10 fold, was somewhat lower than that obtained with optimal concentrations of the potent tumor promoter phorbol myristate acetate (PMA). This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP. In inducing and/or stimulating PA production, the effects of RA and sarcoma virus transformation were synergistic rather than additive. Analogous synergism was observed between RA and PMA, but only at suboptimal concentrations of the latter. RA did not affect PA production in normal or transformed cultures maximally stimulated by PMA. These findings may help to elucidate the role of retinoids in promoting tumor growth, tissue remodeling and teratogenesis.
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PMID:Plasminogen activator in chick fibroblasts: induction of synthesis by retinoic acid; synergism with viral transformation and phorbol ester. 21 37

To explore the generality of the effects of sarcoma viruses, tumor-promoting phorbol esters and retinoic acid, we have studied plasminogen activator production in differentiating chick myogenic cultures. Although slightly higher than in chick fibroblast cultures, the level of spontaneously synthesized enzyme is low; it reaches a peak shortly after maximum cell fusion has been completed and then declines. Rous sarcoma virus (RSV) transformation of differentiating myotubes was accomplished by infecting myoblasts with a temperature-sensitive mutant, maintaining cultures at the nonpermissive temperature until completion of fusion and shifting to permissive temperatures at selected times thereafter. RSV transformation, phorbol myristate acetate (PMA) and retinoic acid all induced high levels of plasminogen activator production by differentiating myotubes in the absence of DNA synthesis. In comparison with fibroblasts, virus-induced enzyme synthesis by myogenic cultures proceeded more slowly but ultimately reached comparably high levels. Whereas cAMP strongly repressed RSV- and PMA-induced plasminogen activator production by chick fibroblasts, it weakly stimulated enzyme synthesis by myotubes. This suggests that enzyme induction by RSV and PMA is not mediated primarily through effects on cAMP metabolism.
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PMID:Plasminogen activator in chick embryo muscle cells: induction of enzyme by RSV, PMA and retinoic acid. 21 22

To explore the interaction of tumor promoters and sarcoma virus transformation with cellular regulatory mechanisms, we have studied induction of plasminogen activator synthesis by these agents in a background of changing cyclic nucleotide concentrations. We have confirmed the original report of Wigler and Weinstein (Nature, 259: 232, 1976) that phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, induces high levels of plasminogen activator production by chick embryo fibroblasts. Sarcoma virus transformation sensitizes the fibroblasts by lowering the threshold concentration for response to the action of PMA, and the effects of transformation and PMA on plasminogen activator synthesis are synergistic rather than additive. The plasminogen activators produced in the PMA-, virus-induced, or synergistically stimulated cultures are indistinguishable. Enzyme production in all three conditions is strongly but reversibly inhibited when cyclic nucleotide levels are raised by exposure to cyclic adenosine-3':5'-monophosphate or cholera toxin. A substantial fraction of the morphological effect that accompanies transformation is not affected by concentrations of cyclic nucleotides that suppress plasminogen activator production, and the two phenomena are therefore at least partially independent expressions of transformation in this system.
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PMID:Modulation of plasminogen activator synthesis in chick embryo fibroblasts by cyclic nucleotides and phorobol myristate acetate. 21 31

Low concentrations of Vitamin A stimulated plasminogen activator synthesis (PA) in chick embryo fibroblasts (CEF). It caused a dose dependent and reversible increase in PA synthesis in both normal CEF and CEF infected with a temperature sensitive mutant of Rous Sarcoma virus (RSV-Ts68). Both induction and deinduction of PA could be inhibited by Actinomycin D. Vitamin A also accentuated the morphological changes associated with transformation in the Rous Sarcoma virus infected cells. The effects of Vitamin A on PA synthesis were essentially similar to those of the known tumour promoter, phorbol myristate acetate (PMA). Both Vitamin A and PMA were found to act synergistically with sarcoma gene expression as far as PA synthesis was concerned.
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PMID:Effect of vitamin A on plasminogen activator synthesis by chick embryo fibroblasts. 23 60

The plasminogen activator (PA) production and the capacity to inhibit embryonic neural retina (NR) cell aggregation by human normal and neoplastic cell lines have been studied. The PA production was detected by both iodinated fibrin and casein lysis assays, and by changes in cell morphology at the presence of activated PA, using dog serum. Since the casein lysis assay and morphological changes proved to be less sensitive than 125I-fibrin lysis assay, a good correlation between these three assays could be observed provided that PA production measured by fibrinolysis exceeded 10--20%. The neoplastic cell lines exhibited the PA production to quite a large extent. The highest fibrinolytic activity (78%) was found in the case of bladder carcinoma cells T24, while the B-5GT cells from giant cell tumor of bone failed to produce any detectable amount of the PA. The cells from synovial sarcoma and both glioma lines exhibited fibrinolytic activity of about 10% and four sarcoma cell lines over the range 20--50%. Out of 13 normal cell lines tested, 7 were negative or exhibited very low fibrinolysis not exceeding 3% of total radioactivity. Four cell lines derived from kidneys, lungs, intestines, and from mixed embryonic tissues showed a marked fibrinolytic activity of about 10--37%, a slightly elevated fibrinolysis being found in embryonic lung cells LEP and cells from fetal skin tissue only at the presence of dog serum. The fibrinolysis detected in the neoplastic cloned cell populations showed considerable differences in the PA production between individual cell clones isolated from the same parental cell line. Unlike the normal fibroblastic cells B-41FB derived from bone, all neoplastic cell lines tested possess the capability to inhibit embryonic NR cell aggregation significantly. The results suggest the effect not to be dependent upon the PA production.
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PMID:Production of plasminogen activator and inhibition of embryonic cell aggregation by cultured human normal and neoplastic cells. 57 60

Hereditary adenomatosis of the colon and rectum (ACR) and its Gardner's syndrome variant, an autosomal dominant trait, indicate a propensity for neoplasia. The present study describes the growth abnormalities of cultured human skin fibroblasts derived from normal-appearing cutaneous biopsies of ACR genotypes and a portion of the clinically asymptomatic ACR progeny, first filial generation, and their differential susceptibility to transformation by Kirsten murine sarcoma virus. These skin fibroblasts, but not cells derived from unaffected individuals, showed lack of contact inhibition, decreased serum requirement for growth, elevated levels of plasminogen activator, and alterations in the intracellular distribution of actin cables; they did not, however, grow in the absence of anchorage, nor did they form palpable tumors in congenitally athymic BALB/c nu/nu mice, and they were normal with regard to cholesterol feedback regulation. Skin fibroblasts from ACR subjects were 100- to 1000-fold more susceptible to transformation by the Kirsten murine sarcoma virus than were normal cells. The virally transformed skin fibroblasts were anchorage-independent and formed tumors in athymic mice. These growth abnormalities represent steps in the changing phenotypic expression of cells undergoing neoplastic transformation. Identification of abnormal expressions associated with oncogenesis may facilitate their use as diagnostic indices for the detection of latent forms of colon cancer in man.
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PMID:Phenotypic markers in human skin fibroblasts as possible diagnostic indices of hereditary adenomatosis of the colon and rectum. 92 93

The human sarcoma cell line HT1080 was found, by in situ hybridization, to consist of cells expressing various levels of urokinase (uPA) and tissue type (tPA) plasminogen activator (PA) suggesting clonal variation of expression of these genes. Colonies originating from single HT1080 cells were, therefore, established and screened for PA activity using a fibrin agarose overlay. Colonies inducing lysis (clone C+ and H+) or no lysis (clones B- and M-) were isolated and tested for mRNA levels of uPA, tPA, uPA receptor (uPAR) and the 3 PA inhibitors (PAI), PAI-1, PAI-2 and protease-nexin I. The different clones revealed considerable variation of expression of the different PA and PAI genes, with lysis-inducing clones expressing mainly the PA genes, whereas non-lysing clones demonstrated higher expression of the PAI genes. Amplification or loss of specific genes was excluded by Southern blotting. The protein levels of cellular and secreted PA and PAI determined by ELISA and Western blots demonstrated a pattern similar to that observed for PA and PAI mRNA concentrations, suggesting clonal differences either on the level of transcription or in RNA processing and/or stability. Due to complex interactions between PA and PAI, neither mRNA nor protein levels of the different genes were predictive for the amount of functional PA activity present in the supernatant or on the cell surface of the different clones. Receptor-bound uPA activity was found to be considerably higher in lysis-inducing than in non-lysing clones and the activity was dependent on neutralization by PAI-1 rather than on the level of uPAR mRNA.
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PMID:Clonal variation of expression of the genes coding for plasminogen activators, their inhibitors and the urokinase receptor in HT1080 sarcoma cells. 132 52

The plasminogen activator was purified to the extent of 150-fold from 20,000 x g supernatant of Yoshida ascites Sarcoma by ammonium sulphate precipitation at 33% saturation followed by affinity chromatography on p-aminobenzamidine-Sepharose 4B. The specific activity of the purified activator was 10,260 IU/mg expressed in terms of International units of urokinase, the known activator of plasminogen. The activator was homogeneous by polyacrylamide slab gel electrophoresis with an apparent molecular weight 75 kDa by gel filtration on Sephadex G-100. Analysis by SDS-polyacrylamide gel electrophoresis under reducing conditions, revealed the presence of two subunits of about 48 and 29 kDa. The activator displayed binding preference to fibrin and was immunologically distinguishable from urokinase, indicating that it could be of non-urokinase origin. The preparation further revealed similarity to standard tissue plasminogen activator with respect to fibrin binding and immunological cross reactivity.
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PMID:Isolation and purification of plasminogen activator from Yoshida ascites Sarcoma of rats. 190 68

Immobilized vitronectin was found to bind both purified plasminogen activator inhibitor type 1 (PAI-1) and the PAI-1 in conditioned culture medium of human sarcoma cells. Similarly, immobilized PAI-1 bound both purified vitronectin and vitronectin from normal human serum. These interactions were demonstrated using both enzyme immunoassay and radioiodinated proteins. Solid-phase vitronectin bound PAI-1 with Kd 1.9 x 10(-7) M, and the reverse interaction gave a Kd 5.5 x 10(-8) M. Evidence was also found for a second type of binding with a Kd below 10(-10) M. The molar ratios of the two proteins in the complex at the saturation levels were approximately one molecule of soluble PAI-1 bound per three molecules of immobilized vitronectin and approximately one molecule of soluble vitronectin being bound per one molecule of immobilized PAI-1. Binding of PAI-1 to vitronectin did not lead to an irreversible loss of the ability of PAI-1 to inhibit urokinase (u-PA) and tissue-type plasminogen activator (t-PA). Active u-PA released vitronectin-bound 125I-labeled PAI-1 radioactivity, suggesting that u-PA interacts with the complex. The Mr 50,000 urokinase cleavage product of PAI-1 also bound to vitronectin, but this bound fragment did not inhibit u-PA. Binding of PAI-1 to vitronectin did not interfere with the ability of vitronectin to promote the adhesion and spreading of cells. These results suggest that the interaction between vitronectin and PAI-1 may serve to confine pericellular u-PA activity to focal contact sites where cells use proteolysis in regional detachment.
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PMID:Interaction of plasminogen activator inhibitor (PAI-1) with vitronectin. 246 12


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