Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth of the human breast cancer cell line MCF-7 is known to be inhibited both by antiestrogens such as 4-hydroxytamoxifen (OHTAM) and by retinoic acid (RA). Uncloned MCF-7 cells (UNC) and two cloned sublines, one sensitive to antiestrogens (E-3) and the other resistant to them (RR), were used in this study. Growth of UNC and E-3 was inhibited by either OHTAM (10(-7) M) or RA (10(-6) M), and this inhibition could not be overcome by the simultaneous addition of estradiol. Subline RR, which was originally selected for resistance to tamoxifen, was resistant to both OHTAM and RA as measured by either growth in culture or colony forming ability. RR was resistant to RA at all concentrations tested between 10(-9) M and 10(-6) M. The inhibition of uncloned MCF-7 cells by RA was dose dependent between 10(-9) M and 10(-6) M. Subline E-3, however, exhibited a mixed response to RA. At 10(-9) M and 10(-8) M, growth was stimulated, but at 10(-7) M and 10(-6) M it was inhibited. The level of estrogen receptor was measured in the same experiment by using a whole cell assay. In the uncloned MCF-7 cultures and in both the RR and E-3 sublines the level of estrogen receptor was increased between 50 and 200% by RA. The production of plasminogen activator by MCF-7 cells is stimulated by estrogen. RA had a dual effect on plasminogen activator production. In the absence of estrogen, RA inhibited production below the unstimulated level, but in cells stimulated by estrogen, RA increased plasminogen activator production. The results reported here support possible interactions between the mechanisms by which cells respond to estrogen, antiestrogens, and retinoids.
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PMID:Responses to retinoic acid of tamoxifen-sensitive and -resistant sublines of human breast cancer cell line MCF-7. 142 59

Liarozole reduced tumor growth in the androgen-dependent Dunning-G and the androgen-independent Dunning MatLu rat prostate carcinoma models as well as in patients with metastatic prostate cancer who had relapsed after orchiectomy. In vitro, liarozole did not have cytostatic properties, as measured by cell proliferation in breast MCF-7 and prostate DU145 and LNCaP carcinoma cell lines. It did not alter the metabolism of labeled testosterone i.e. the 5 alpha-reductase in cultured rat prostatic cells. In mouse F9 teratocarcinoma cells liarozole did not show any retinoid-like properties but enhanced the plasminogen activator production induced by retinoic acid. Furthermore, liarozole and retinoic acid similarly reduced the growth of the androgen-dependent Dunning-G tumor in nude mice and inhibited tumor promotion elicited by phorbol ester in mouse skin. These data have raised the hypothesis that the antitumoral properties of liarozole may be related to inhibition of retinoic acid degradation, catalyzed by a P-450-dependent enzyme that is blocked by the drug.
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PMID:Experimental studies with liarozole (R 75,251): an antitumoral agent which inhibits retinoic acid breakdown. 152 60

LY117018 is a non-steroid anti-estrogen which exhibits about 100 times higher affinity for estrogen receptor than tamoxifen, another anti-estrogen. The cell line ES-1, which was isolated from human breast cancer MCF-7 cells, was highly sensitive to the cytocidal action of estradiol. Growth of ES-1 cells was inhibited by 10(-8)M 17 beta-estradiol, a concentration that stimulated the growth of parental MCF-7 cells. The estradiol-induced growth inhibition of ES-1 cells was almost completely reversed by treatment with LY117018, but not by treatment with tamoxifen. The relative binding affinity of LY117018 for estradiol receptor was equal to that of estradiol in both MCF-7 and ES-1 cells. Treatment of ES-1 cells with estradiol specifically induced tissue-type plasminogen activator (t-PA), whereas such estradiol-induced activation was not observed in parental MCF-7 cells. Quantitative immunoreactive assays and Northern blot analysis showed that estradiol-induced expression of t-PA was blocked by LY117018 in ES-1 cells. The inhibitory effect of tamoxifen was about 100 times lower than that of LY117018. The inhibition of t-PA gene expression by LY117018 might be due to competitive inhibition with estradiol in estradiol receptor binding.
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PMID:Counteraction of estradiol-induced activation of tissue-type plasminogen activator in a human breast cancer cell line by an anti-estrogen, LY117018. 170 5

ES-1 cells, which showed a higher sensitivity to the cytocidal action of estradiol were isolated from a human breast cancer MCF-7 cell line. Growth of ES-1 cells was inhibited by a dose of 17-beta estradiol that stimulated the growth of the parental MCF-7 cells. Proteins secreted from MCF-7 and ES-1 cells when cultured with 17-beta estradiol were compared by sodium dodecyl sulfate-containing polyacrylamide gel electrophoresis (SDS-PAGE). Addition of estradiol to culture medium enhanced secretion of a protein of molecular mass of 52 kDa in media for both MCF-7 and ES-1 cell lines, but the secretion of a second 67 kDa protein was enhanced about 10-fold only in ES-1 cells. The analysis by SDS-PAGE of culture medium immunoprecipitated with anti-tissue-type plasminogen activator (t-PA) antibody demonstrated that the band of 67 kDa protein specifically secreted from estradiol-treated ES-1 cells contained t-PA. Zymography assays, quantitative immunoreactive assays, and Northern analysis showed about 5-fold specific increase by estradiol of t-PA with molecular mass of 65-70 kDa in ES-1 but not in its parental MCF-7 cells. Cellular level of the plasminogen activity was also specifically enhanced in ES-1 cells by estradiol, but only a slightly in MCF-7 cells. By contrast, another urokinase-type PA (u-PA) with molecular weight of 55 kDa showed very low level activity in both MCF-7 and ES-1 cell lines in the presence of estradiol. Formation of t-PA mRNA was specifically enhanced in ES-1 cells when ES-1 cells were treated for more than 12 h with 10(-8) M 17-beta estradiol. Estradiol did not elongate the lifetime of t-PA mRNA in ES-1 cells. A unique phenotype of ES-1 cells in response to estradiol is discussed in relation to activating expression of the t-PA gene.
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PMID:Enhanced production of tissue-type plasminogen activator by estradiol in a novel type variant of human breast cancer MCF-7 cell line. 211 58

Understanding of the leukemic evolution of human non-Hodgkin's lymphomas is hindered by the lack of appropriate animal models. For this purpose, a highly leukemic cell line NQ22, derived from a MCF 247 murine leukemia virus (MuLV)-induced murine T-cell lymphoma, was established, and its preliminary characterization is described. The NQ22 cell line is easily transplantable subcutaneously (s.c.) into syngeneic AKR mice exhibiting early peripheral blood invasion and widespread dissemination with a leukemic pattern of infiltration. Such peculiar in vivo behavior is a stable phenotypic feature, probably determined genetically. Biological and differentiation characteristics of the NQ22 cell line were analyzed and compared to those of other non-leukemic T-lymphoma lines. In addition, no evidence of possible involvement of plasminogen activator (PA) enzymes and of their inhibitors (PAI) in the spreading ability of NQ22 cells was observed.
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PMID:Establishment and characterization of a leukemic murine cell line derived from MCF 247 MuLV-induced T-cell lymphoma. 215 41

We have analyzed the plasminogen activator (PA) systems of two metastatic breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, as a function of 17 beta-estradiol stimulation when the cells were cultured on purified components of extracellular matrix. Laminin enhanced PA levels in both cell lines, but this enhancement seemed to occur via different mechanisms, including dissociation of inhibitor complexes. The major effect was the marked increase in cell-associated urokinase-type PA (u-PA); the increase was independent of estrogen in hormone-insensitive MDA-MB-231 cells grown on laminin-coated surfaces. In estrogen-sensitive MCF-7 cells, 17 beta-estradiol stimulated u-PA secretion in a similar fashion on plastic, laminin, fibronectin, or collagen but acted in synergy with laminin in the production and release of tissue-type PA.
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PMID:Modulation of plasminogen activator systems by matrix components in two breast cancer cell lines: MCF-7 and MDA-MB-231. 249 46

Cytosols of malignant breast tissue contained significantly higher levels of thrombospondin (TSP) and von Willebrand factor (vWF) than non-malignant breast. TSP and vWF content of human breast were significantly correlated whereas there was no correlation between TSP and the platelet-specific protein beta-thromboglobulin (beta TG). Whilst TSP in pre-menopausal breast cancer was slightly lower than in post-menopausal breast cancer, it did not correlate with oestrogen receptors (ER) or progesterone receptors (PR), but was negatively correlated with tissue-type plasminogen activator (tPA), an oestradiol-inducible enzyme. Secretion of TSP by MCF-7 cells was low and refractory to hormones. High levels of TSP appeared to be associated with the centre of the tumour mass. It is suggested that activation of the endothelium may be responsible, at least in part, for the high levels of TSP found in malignant breast tissue and could be a factor in the growth and spread of breast cancer.
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PMID:Thrombospondin in malignant and non-malignant breast tissue. 252 76

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses the estrogen enhancement of tissue plasminogen activator (t-PA) by MCF-7 breast cancer cells. 17 beta-estradiol treatment of MCF-7 cells was previously shown to enhance t-PA secretion in a receptor-mediated process dependent on RNA and protein synthesis. The current studies demonstrate that treatment with TCDD, at a concentration as low as 10(-11) M, reduces the 17 beta-estradiol-induced enhancement of t-PA secretion in these cells. Treatment of MCF-7 cells with TCDD alone does not alter t-PA activity nor was inhibition of t-PA activity observed when TCDD was added directly to the enzyme assay. Kinetic studies and the lack of inhibition following in vitro mixing of conditioned media from TCDD-treated and control 17 beta-estradiol stimulated MCF-7 cells argue against TCDD induction of a plasminogen activator inhibitor. The related polychlorinated dibenzofuran, 2,3,7,8,-tetrachlorodibenzofuran, while also active, is less potent that TCDD. Other polychlorinated dibenzodioxins, polychlorinated dibenzofurans, and polychlorinated biphenyls do not suppress 17 beta-estradiol induction of t-PA over the concentrations tested. These results are in agreement with the structure-activity relationships established using these compounds in other assay systems. Treatment with TCDD does not alter the number or affinity of 17 beta-estradiol receptors of MCF-7 cells. TCDD treatment does not suppress constitutive t-PA activity in the estrogen independent breast cancer line MDA-MB-231 nor the t-PA induced by 12-O-tetradecanoylphorbol-13-acetate in HeLa cells. These effects suggest that TCDD is not acting directly on expression of the t-PA genome. Induction of aryl hydrocarbon hydroxylase by TCDD, a cytochrome P-450 regulated metabolic enzyme for which TCDD is the most potent known inducer, was observed in MCF-7 cells but not in MDA-MB-231 or HeLa cells. A plausible mechanism for the antiestrogenic activity of TCDD is based on the metabolic conversion of 17 beta-estradiol to less active derivatives by TCDD induced cytochrome P-450 metabolic enzymes.
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PMID:Suppression of estrogen-regulated extracellular tissue plasminogen activator activity of MCF-7 cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin. 311 94

The relation of in vitro properties to tumorigenicity was studied using eight sublines of the human breast cancer cell line MCF-7. Four of the eight were tumorigenic in estrogen-treated nude mice. The sublines differed for each of the in vitro properties measured, and no property correlated perfectly with tumorigenicity. Cytochalasin B-induced multinucleation was a property of all four tumorigenic sublines but of only one of the four nontumorigenic ones. Anchorage-independent growth and concanavalin A-mediated hemadsorption levels were higher in all sublines than reported levels for nontransformed fibroblasts and normal human or mouse mammary epithelial cells. The production of both plasminogen activator and a plasminogen-independent fibrinolytic activity showed no relationship to tumorigenicity but was higher in those sublines producing more invasive tumors. It appears that no one of these in vitro properties is sufficient to make a subline tumorigenic. Rather, the first three properties studied here and, perhaps, also production of plasminogen activator may each be necessary, but not sufficient, to make a subline tumorigenic. In addition, properties such as production of plasminogen activator and other proteases, while perhaps not essential to tumorigenicity, may confer characteristics, such as invasiveness, on the tumors produced by a given subline.
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PMID:Relation of in vitro properties to tumorigenicity for a series of sublines of the human breast cancer cell line MCF-7. 377 50

Tamoxifen aziridine (TA), an antiestrogen-based affinity label for the estrogen receptor, is highly selective and efficient in its covalent binding to the estrogen receptor (Katzenellenbogen et al., J. biol. Chem. 258 (1983) 3487-3495). Thus, it was of interest to investigate the biological character and potency of this compound and, in particular, to determine if the irreversible attachment of this tamoxifen-derived compound to the estrogen receptor would result in enhanced antiestrogenic properties or in unusual biological activity. The effect of tamoxifen aziridine and tamoxifen (Tam), the parent compound which is an antiestrogen that binds reversibly to the estrogen receptor, were compared with respect to their effects on uterine growth, growth of dimethylbenzanthracene (DMBA)-induced mammary tumors in rats, and proliferation and plasminogen activator activity of MCF-7 human breast cancer cells. In immature (day 20) rats, Tam and TA behaved as weak estrogen agonists and estrogen antagonists in that Tam or TA alone increased uterine weight to levels lower than that evoked by estradiol (E2), and both were able to suppress the stimulation of uterine weight evoked by E2. Administration of Tam and TA via Alzet minipumps (25 or 200 micrograms/rat/day) to mature rats bearing DMBA-induced mammary tumors resulted in marked regression and/or disappearance of most tumors. Uterine weights were also suppressed in these mature rats by Tam and TA. Tam was slightly more potent than TA in evoking tumor regression and in suppressing uterine weights in these in vivo studies. In MCF-7 human breast cancer cells in culture, Tam and TA suppressed cell proliferation and evoked no increase in plasminogen activator activity by themselves, while being very effective in preventing plasminogen activator activity stimulation by E2. Thus, TA displayed a bioactivity profile similar to that of Tam, the reversibly binding ligand, in vitro and in vivo. The covalent attachment of TA to the receptor does not, therefore, markedly alter the biological character or potency of the antiestrogen receptor complex.
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PMID:Biological activities of tamoxifen aziridine, an antiestrogen-based affinity label for the estrogen receptor, in vivo and in vitro. 393 47


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