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)

The content of PAI-I was measured in carcinoma tissues from the stomach and colorectum divided macroscopically into 3 portions: the central part of the carcinoma, the marginal part of the carcinoma containing some normal mucosa, and the normal mucosa. Among these tissues, the highest levels of PAI-I antigen were found in the central part of the carcinoma. On the other hand, no PAI-I antigen or activity was observed in the normal mucosae. The PAI-I produced in the stomach and colorectal carcinoma tissues showed a non-lytic zone with a molecular weight of 54 kDa by reverse fibrin autography, and this 54-kDa band reacted with anti-PAI-I IgG on an immunoblotted nitrocellulose membrane by the avidin-biotin complex method. The contents of PAI-2 in the carcinoma tissues were not significantly different from those in the normal mucosa of the stomach and colorectum. In both the stomach and colorectal carcinomas, the highest value of u-PA/total PA (sum of u-PA and t-PA) was observed in the central part of the carcinoma, followed by the marginal part of the carcinoma, and was lowest in the normal mucosa. We conclude that increased levels of PAI-I in malignant tissue of the stomach and colorectal tract may serve to modulate extra-cellular proteolysis by u-PA.
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PMID:Plasminogen activator inhibitor 1 in human carcinoma tissues. 190 4

Malignant tumors are generally characterized by extensive local tissue invasion and destruction of ECM which may be due to increased constitutive expression and activity of secreted proteases. Moreover, a large number of diverse protease activities may be constitutively over-expressed in a simultaneous or co-ordinated fashion, thereby significantly increasing cellular invasive potential of the cells. To explore this relationship, we have measured steady-state levels of mRNA coding for urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), transin and tissue-specific inhibitor of metalloproteinases (TIMP); as well as gelatinolytic, caseinolytic and plasminogen activator activities secreted by SPI, a non-metastatic mouse mammary carcinoma cell line and 4 metastatic sublines derived from it. mRNA encoding metalloproteinase transin was increased 15- to 20-fold, while TIMP transcripts were decreased 3-fold in the metastatic sublines compared to parental SPI tumor cells. Metastatic sublines secreted higher levels of gelatinase (i.e., 92 kDa and 64 kDa) as well as proteases with caseinolytic activity (i.e., 115 kDa and 57 kDa) when compared with SPI cells. Moreover, these enzymes were identified as neutral metalloproteinases. Although the amount of uPA mRNA appeared to be the same in SPI and the metastatic sublines, the latter secreted 1.5-3 times more uPA activity into the culture supernatants. Metastatic competence in the SPI tumor model is therefore associated with increased secretion of several metalloproteinase activities and uPA, as well as decreased TIMP expression, consistent with a more invasive phenotype.
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PMID:Constitutive expression and secretion of proteases in non-metastatic SP1 mammary carcinoma cells and its metastatic sublines. 204

Carcinoma of the bile duct at the hepatic hilar region is not a rare condition but with a low resectability rate. The incidence of this disease seems to be on increasing. In a previous report, 60 cases were explored surgically from 1975 to 1985, but resection was only possible in 5 cases (9.1%); while in the recent years from June, 1986 to June 1989, 24 cases were explored in the Surgical Department of General Hospital of PLA, 16 cases were resected, with a resectability rate of 66%. The increase of resectability rate was due to earlier recognition of this condition and the extension of surgery, including major resection of liver as well as radical dissection of the hepato-duodenal ligament and reparative operations on the blood vessels. Among these 16 cases, major hepatic resection was performed in 10 cases, in which, 3 cases of resections of the middle lobe of the liver were done instead of right or extended right lobectomy. No operative mortality in the 30 days' postoperative period, but the postoperative morbidity rate was still high and most of the complications were related to biliary leakage and infect ion. Three patients died in the postoperative follow up period at 6.14 and 15 months respectively. All of them died from biliary infection. The remaining 13 patients were still living, the longest being 40 months and the average living time was 16.1 months. Probably, lowering of the operative mortality rate and morbidity rate are still the most important considerations in the surgical treatment of hilar carcinoma at the present time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Surgical treatment of hilar bile duct carcinoma]. 208 22

Plasminogen activator inhibitor-type 1 (PAI-1) was identified in extracts of Lewis lung carcinoma, and its immunohistochemical localization was studied together with that of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators. All primary tumors (n = 11) contained heterogeneously distributed immunoreactivity against each of the three components. Most often, areas that contained u-PA immunoreactivity also contained PAI-1 immunoreactivity. However, several areas showed a strong u-PA immunoreactivity, but no or low PAI-1 immunoreactivity. The latter staining pattern was only found in peripheral areas, and usually in areas with histological signs of tissue destruction. Lung metastases always contained u-PA immunoreactivity, while PAI-1 immunoreactivity was found in most, but not all, metastases. t-PA immunoreactivity was found in a few scattered tumor cells, in primary carcinomas as well as metastases. Controls that included absorption with highly purified antigen preparations and immunoblotting, indicated that all the immunoreactivity represented genuine PAI-1, u-PA and t-PA, respectively. The results are consistent with an assumption that the plasminogen activation system, and particularly u-PA and PAI-1, plays a role in regulation of breakdown of extracellular matrix proteins during invasive growth in this carcinoma.
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PMID:Plasminogen activator inhibitor-type 1 in Lewis lung carcinoma. 210 45

The activity of plasminogen activator (PA) in tissue extracts from nasopharyngeal carcinoma (NPC) was determined by means of the fibrin plate method. Development of PA activity was observed in 16 out of 25 cases investigated. Furthermore, using tissue extract of NPC with PA activity, characterization and identification of the activator were carried out by means of electrophoretic analysis, fibrin zymography and immunological analysis. The molecular weight of this PA was found to be 38,000 daltons. Additionally, a urokinase type of plasminogen activator was contained in the tissue extracts.
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PMID:Identification of a plasminogen activator derived from nasopharyngeal carcinoma. 212 77

Acquisition of cell motility is often correlated with the malignant progression of a transformed cell. To investigate some of the mechanisms involved in the development of a migratory state, we transfected the NBTII rat carcinoma cell line, which forms stationary epithelial clusters in culture, with the gene encoding human transforming growth factor alpha (TGF alpha). Expression of TGF alpha in NBTII cells resulted in cells of motile and vimentin-positive phenotype with internalized desmosomal components, analogous to the treatment of cells with exogenous TGF alpha. The clones expressed a 5.2-kb TGF alpha message and synthesized an 18-kDa form of TGF alpha. Supernatants of TGF alpha-producing clones induced the internalization of desmosomal components, the production of vimentin, and increased motility in untransfected epithelial NBTII cells, indicating that the factor produced by the clones was in a biologically active form. TGF alpha-producing clones secreted significant levels of a 95-kDa gelatinolytic metal-loproteinase, virtually absent in untransfected cell supernatants. In contrast, levels of inhibitors of metalloproteinases and of a plasminogen activator were similar in untransfected and TGF alpha-transfected NBTII cells. These results suggest that expression of TGF alpha in an epithelial tumor cell results in the development of a motile, fibroblast-like phenotype with matrix-degrading potential, which could result in a more aggressive tumor in vivo.
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PMID:Expression of transfected transforming growth factor alpha induces a motile fibroblast-like phenotype with extracellular matrix-degrading potential in a rat bladder carcinoma cell line. 213 46

Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PAP), von Willebrand factor antigen (vWF:Ag) plasminogen activator antigen (PA) and plasminogen activator inhibitor-1 antigen (PAI-1), were determined in 110 patients with arterial thromboembolic diseases within 4 weeks after attack (Th; 41 cases with myocardial infarction and 69 with cerebral infarction), 67 patients with various types of carcinoma (Ca; 31 cases without metastasis and 36 with metastasis) and 50 age-matched healthy individuals (Co). The following results were obtained: 1) Mean plasma levels of TAT, PAP, vWF:Ag, PA and PAI-1 were significantly higher in Th than Co. 2) Mean plasma levels of TAT, PA and PAI-1 were significantly higher in Ca than Co regardless of metastasis but those of PAP and vWF:Ag were significantly higher only in Ca with metastasis than Co. 3) Significant relationship was observed between plasma levels of TAT and PAP both in Th and Ca. 4) Significant relationship was also observed between plasma levels of TAT and vWF:Ag, PA or PAI-1 in Th, but not in Ca. It is suggested from these results that the coagulopathies observed in these patients result from the activation of intravascular blood coagulation and fibrinolysis, and that vascular endothelial cell damage may play an important role in the activation in Th.
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PMID:Studies on the pathogenesis of coagulopathy in patients with arterial thromboembolism and malignancy. 214 28

The amino terminal portion of urokinase type plasminogen activator (uPA) interacts with a cell surface binding protein/receptor that recognizes a region of the molecule autonomous from that of the catalytic domain of the enzyme, which mediates the conversion of plasminogen to plasmin. The expression of cell surface uPA receptors (uPA-Rs) and their association with uPA have been implicated in cellular invasion and tissue destruction. Treatment of A431 squamous carcinoma cells (SqCC) with epidermal growth factor (EGF) has previously been shown to result in an induction of the synthesis and extracellular accumulation of uPA and the plasminogen-dependent proteolysis of extracellular matrix (ECM). Regulation of cell membrane associated uPA activity by EGF and its influence on uPA-R expression in A431 cells, which possess an unusually large number of EGF-R (greater than 10(6)), and in an EGF-R expression variant (A431/A5), which contains 20-fold fewer cell surface EGF-R, were assessed. Exposure to 5-50 ng/mL of EGF for 24 hr enhanced uPA activity 2- to 3-fold in partially purified membrane preparations derived from A431 cells in a concentration dependent manner. In contrast, no changes in tissue type plasminogen activator (tPA) activity were detected under similar conditions. A431/A5 cell membrane preparations did not exhibit such an EGF mediated response. In accord with EGF enhanced uPA activity, a 2-fold increase in immunoreactive cell surface associated uPA was observed in A431 cells using indirect immunofluorescence staining. The increase in cell surface uPA produced by exposure to EGF required protein synthesis and could be blocked by cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of human squamous cell carcinoma plasma membrane associated urokinase plasminogen activator by epidermal growth factor. 216 31

Activities of cathepsin B, cathepsin L, and plasminogen activators (urinary type plasminogen activator and tissue type plasminogen activator) were assayed in homogenates of cancer tissue, normal tissue closely surrounding the cancer tissue, and normal tissue distant from the cancer tissue from 30 patients undergoing surgery for gastric cancers and 10 patients undergoing surgery for colon cancers. Activities of those proteases were also assayed in homogenates of adenoma tissue from 10 patients undergoing polypectomy for colon polyps. In the gastric cancer tissue homogenates, the activities of cathepsin B, cathepsin L and tissue type plasminogen activator were significantly higher than in normal tissues. By contrast, the activities of urinary type plasminogen activator of gastric cancer tissues were significantly lower than normal tissues. In the colon cancer tissue homogenates, the activities of cathepsin, B, cathepsin L, and urinary type plasminogen activator were significantly higher than in normal tissues. On the other hand, the activities of tissue type plasminogen activator of cancer tissues were significantly lower than normal tissues. But there were no significant differences in the activities of plasminogen activators between the cancer tissues and adenoma tissues. These results suggest that cathepsin B and cathepsin L play an important role in gastric and colon cancer proliferation and evolution, although the roles of plasminogen activators in gastric and colon cancer proliferation and evolution and in the colon adenoma-carcinoma sequence are still unknown.
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PMID:[Protease activities in gastric and colon cancer tissues]. 223 1

The anchorage-dependent and anchorage-independent growth of the human mammary carcinoma cell line MDA-MB-231 is inhibited by vitamin A (retinol). Clones resistant to growth inhibition by retinol were isolated from this cell line in soft agar without the use of mutagens. This paper describes the isolation and characterization of the resistant lines. The clones were selectively resistant to retinol. There was significant growth inhibition after treatment with retinoic acid and 13-cis-retinoic acid. The resistant clones maintain their resistance to retinol through multiple passages. Resistance is specific for inhibition of growth, because treatment of the resistant clones results in stimulation of plasminogen activator activity without alteration of proliferation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows no significant qualitative or quantitative difference in the clones when compared with the MDA-MB-231 parent line. Although the clones do not regrow in soft agar, they are tumorigenic in athymic mice. Tumors are produced at a rate similar to the parent line. The advantage of this isolation method is that sensitive and resistant malignant cells derived from the same parent cell line are now available to study the molecular events involved in the inhibition of cellular proliferation after treatment with retinol.
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PMID:Selective isolation of human breast carcinoma cells resistant to the growth-inhibitory effects of retinol. 236 35


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