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)

Biopsy specimens of human brain metastases were examined for amplification and expression of the proto-oncogene c-erbB1 (located on chromosome 7) encoding the epidermal growth factor receptor (EGFR). Moreover, the tumour DNA was also examined for amplification of other cancer-related genes on this chromosome: the proto-oncogene c-met, the gene for platelet-derived growth factor A-chain, and the gene for plasminogen activator inhibitory type 1. All 18 brain metastases demonstrated positive binding of biotinylated EGF on cryosections. Three out of 18 metastases had amplification of the EGFR gene; the other chromosome-7 genes tested were not amplified. Thus, an increased EGFR gene expression seems to be a general finding in a wide range of carcinomas metastatic to the brain, whereas we found only occasional selective EGFR gene amplifications in single cases.
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PMID:Expression of the epidermal growth factor receptor gene in human brain metastases. 152 Apr 84

The total plasminogen activator (PA) activity and the activities of urokinase type (uPA) and tissue type (tPA) plasminogen activators were measured in 43 primary human breast cancer homogenates. The majority of the PA activity was found in the 100,000 X g crude membrane pellets (log mean of 490 milli-IU/mg of protein, +1169, -346), and little PA activity was present in the cytosolic supernatant (log mean of 19 milli-IU/mg of protein, +168, -17). The activities of total PA and of each type of PA were compared to the estrogen receptor (ER) and epidermal growth factor receptor (EGFR) status of the tumors and to their histological grade. Total PA activity and uPA activity were not significantly different in any group of tumors stratified according to receptor status or tumor grade. Tissue type PA levels, however, were significantly lower in ER-negative compared with ER-positive tumors and in EGFR-positive compared with EGFR-negative tumors (P less than 0.01 and less than 0.05, respectively). The tPA activity was also related to grade, decreasing with worsening differentiation (P = 0.04). The ER-negative tumors were further stratified into EGFR-positive and -negative subgroups. Only the ER-negative tumors possessing EGFR had significantly lower tPA levels than the ER-positive tumors (P less than 0.01). Low tPA levels in breast cancers were, therefore, associated with ER negativity combined with EGFR positivity and may be an indication of poorer differentiation and prognosis.
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PMID:Relationship of membrane-bound tissue type and urokinase type plasminogen activators in human breast cancers to estrogen and epidermal growth factor receptors. 314 Oct 47

Human transforming growth factor type alpha (TGF-alpha) was synthesized by a stepwise solid-phase method with an overall yield of 26%. Synthetic TGF-alpha, consisting of 50 amino acid residues deduced from a cDNA precursor sequence, was purified in a single HPLC step. The homogeneity and primary structure were confirmed by several criteria including Edman degradation and mass spectrometry. Synthetic TGF-alpha was as active as murine epidermal growth factor in binding to the epidermal growth factor receptor and in stimulation of anchorage-dependent and of anchorage-independent growth of normal indicator cells in culture. Synthetic TGF-alpha stimulated plasminogen activator production in A 431 and HeLa cells; the stimulation was similar to that induced by epidermal growth factor. Furthermore, synthetic human TGF-alpha showed similar immunoreactivity when compared with rat TGF-alpha. Thus, the 50-amino acid TGF-alpha is likely to be the bioactive principle produced and secreted by tumor cell lines.
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PMID:Efficient synthesis of human type alpha transforming growth factor: its physical and biological characterization. 349 Jun 62

The characteristics of RME-5-3-1 cell line, which had been established from C3H/He mouse embryos by culture in benzaldehyde-containing medium, were compared with those of a benzaldehyde-untreated cell line, RME-5-1, derived from the same embryos as the former and with those of RME-5-1/TMT cell line, reestablished from the tumors induced by implantation of RME-5-1 cells into syngeneic mice. The characterization of these cell lines covered cell morphology, chromosome distribution, population doubling time, saturation density, fibronectin, epidermal growth factor receptor, plasminogen activator, ornithine decarboxylase, anchorage-independent growth and transplantability into mice. The results indicated that RME-5-3-1 cells had well-preserved normal phenotypes, while both RME-5-1 and RME-5-1/TMT cells showed malignant phenotypes to varying degrees.
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PMID:Characteristics of C3H/He mouse embryo cell lines established by culture with or without benzaldehyde. 698 89

The regulatory effects of transforming growth factor (TGF)-alpha on phospholipase A(2) (PLA(2)) isozymes contributing to prostaglandin generation in rat gastric epithelial RGM1 cells were examined. Stimulation with TGF-alpha for 24 h time-dependently induced prostaglandin E(2) generation with an increase in cyclo-oxygenase-2 protein. The TGF-alpha-induced prostaglandin E(2) generation was suppressed by NS-398, a cyclo-oxygenase-2 inhibitor. TGF-alpha stimulated the activity and the protein synthesis of cytosolic PLA(2) (cPLA(2)). A time-dependent increase in cPLA(2) protein occurred in parallel with PGE(2) generation, which was inhibited by methyl arachidonyl fluorophosphonate (MAFP), a cPLA(2) inhibitor. However, no change in activity of secretory PLA(2) or Ca(+2)-independent PLA(2) was observed in the TGF-alpha-stimulated cells. Stimulation with the Ca(2+) ionophore A23187 for 10 min induced MAFP-sensitive arachidonic acid liberation. Interestingly, preincubation with TGF-alpha for 24 h diminished A23187-stimulated arachidonic acid liberation despite the increase in cPLA(2) protein. Under the conditions, TGF-alpha was found to increase p11, an endogenous cPLA(2) suppressor, also known as annexin II light chain. The TGF-alpha-induced increase in p11 was suppressed by tyrphostin AG1478, an inhibitor of tyrosine kinase of epidermal growth factor receptor, which was also found to restore the inhibition by TGF-alpha of A23187-stimulated arachidonic acid liberation. However, TGF-alpha did not alter protein levels of annexin II heavy chain. These results suggest that TGF-alpha stimulates prostaglandin generation through an increase in cPLA(2), the hydrolytic action of which may be under the control of p11.
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PMID:Transforming growth factor-alpha stimulates prostaglandin generation through cytosolic phospholipase A(2) under the control of p11 in rat gastric epithelial cells. 1105 23

In order to investigate the possible hormone-dependence of CD44v6 in human breast cancer, we assayed the concentrations of this isoform in the membrane fraction of 168 invasive ductal carcinomas (IDC) and in 26 normal breast tissue samples, 18 fibradenomas (FAD), 3 fibrocystic disease specimens (FD), 7 mucinous carcinomas and 4 medullary carcinomas using the ELISA method. The results were compared with those of the estrogen (ER) and progesterone (PR) receptors, pS2, tissue type plasminogen activator (t-PA), cathepsin D, epidermal growth factor receptor (EGFR) and c-erbB2/neu oncoprotein concentrations. Menopausal status, size of the tumor in the cases of cancers, axillary lymph node involvement, histologic grade, ploidy, cellular synthesis phase, multifocality and multicentricity were also considered as variables. The cut-off value for CD44v6-positivity was set at 5 ng/mg prt. membrane protein content. 64/138 (38.1%) infiltrating ductal carcinomas scored positive. This was significantly higher than for the normal breast tissue (0/26; p: 0.0001), similar to that seen in the FAD (3/18), fibrocystic disease (0/3), infiltrating mucinous carcinomas (4/7) and lobular (3/15) and significantly lower than for the infiltrating medullary carcinomas (4/4; p: 0.027). There were no significant differences with the other groups of tissues studied. Furthermore, CD44v6-positive IDC showed significantly higher concentrations of ER, PR and cathepsin D and lower (p: 0.051) concentrations of EGFR when compared to their CD44v6-negative counterparts. The significant coexpression of ER, PR and cathepsin D seems to indicate a possible role for hormonal regulation of CD44v6 expression while the role of pS2 and t-PA, estrogen related proteins, was very reduced.
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PMID:[Expression of the adhesion molecule CD44v6 in infiltrating ductal carcinomas of the breast is associated with hormone dependence. Our experience with 168 cases]. 1106 11

Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and inhibitor, plasminogen activator-type 1 (PAI-1) are proposed to be of prognostic significance in some cancers. To determine the prognostic value of the urokinase plasminogen activation system in ovarian cancer, levels of uPA, uPAR, and PAI-1 were measured in extracts of ovarian cancer tissue using ELISA tests. uPA and PAI-1 were determined in 70 tumor extracts and uPAR in 43 extracts. Levels were correlated with age, tumor histology, stage, grade, lymph node and metastatic status, residual disease, risk of recurrence, epidermal growth factor receptor (EGFR) expression, cathepsin D (Cath-D), and c-erbB-2 levels. uPA and uPAR did not exhibit correlation with any of these parameters. However, patients with high grade tumor, recurrence, and lower EGFR and Cath-D had significantly higher PAI-1 levels compared to those of others (P < 0.05). Kaplan-Meier plots of survival were compared. uPA and uPAR were not related to disease-free or overall survival. Although low PAI-1 appeared to predict a longer overall survival, the difference was not statistically significant. Multivariate analysis revealed that PAI-1 was a predictor for overall survival although it was not as strong as stage. These results suggest that elevated PAI-1 seems to be correlated with an unfavorable prognosis in ovarian cancer.
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PMID:Clinical relevance of urokinase-type plasminogen activator, its receptor and inhibitor type 1 in ovarian cancer. 1124 Jul 1

In order to study the association of histological grade (HG) with specific clinical and biological parameters which may influence the clinical behavior of infiltrating ductal carcinomas of the breast (IDC), we analyzed in 229 tissue samples the cytosolic concentrations of estrogen receptor (ER), progesterone receptor (PR), pS2, cathepsin D, hyaluronic acid (HA) and tissue-type plasminogen activator (t-PA), as well as those of the erbB2 oncoprotein, epidermal growth factor receptor (EGFR), HA, CD44v5 and CD44v6 in the cell membrane fraction. Likewise, we considered size, ploidy, S-phase fraction and axillary node involvement as variables of the study. The transition from HG1 to HG2 and from HG2 to HG3 was accompanied by a number of common features: global increase in size, greater number of tumors >2.0 cm, decrease in membrane hyaluronic acid concentrations, increased cell proliferation (S-phase >7%) and greater aneuploidy. Other events observed during the transition from HG2 to HG3 were a decrease in ER, PR, t-PA and cytosolic hyaluronic acid. These results led us to consider that HG is associated with certain clinical-biological changes that may help explain its value as a prognostic factor in breast carcinomas.
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PMID:Histological grade in breast cancer: association with clinical and biological features in a series of 229 patients. 1128 57

Cell contact with the extracellular matrix component, hyaluronan, plays a pivotal role in glioma cell invasion and proliferation. Although it is well established that glioma cells can bind hyaluronan to their surface via the expression of CD44, the cellular responses following ligand-receptor interaction remain poorly understood. Given that a large proportion of human high grade gliomas over express the epidermal growth factor receptor (EGFR) and ErbB2, this study aimed to investigate whether an interaction exists between CD44 and these receptor tyrosine kinases. Here we present evidence that CD44 co-immunoprecipitates with EGFR and ErbB2 in the glioma cell lines U87MG and SMA560. Hyaluronan treatment mediated the rapid and transient phosphorylation of extracellular signal regulated kinases 1 and 2 (ERK1 and ERK2) in glioma cell lines. This response to hyaluronan was augmented by the co-expression of EGFR. EGFR also differentially modified the hyaluronan induced expression of a number of genes associated with cellular invasion and proliferation. Northern blot analysis demonstrated that genes encoding urokinase type plasminogen activator (uPA), urokinase type plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases (TIMP-1) and c- myc were up-regulated in response to hyaluronan. Furthermore, zymographic analysis revealed increased levels of uPA in the conditioned medium of hyaluronan stimulated cells. These results indicate a novel functional relationship between CD44 and EGFR in glioma cell lines. The capacity of CD44 to form stable complexes with receptor tyrosine kinases may provide a versatile system for the regulation of cellular invasion and proliferation that allows hyaluronan to activate signal transduction pathways and modulate gene expression via an EGFR-dependent manner. These findings provide new insights into the mode by which hyaluronan regulates the malignant phenotype and also suggest a role for EGFR-CD44 interactions in glial tumorigenesis.
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PMID:EGF receptor modifies cellular responses to hyaluronan in glioblastoma cell lines. 1209 35

The expression and activity of epithelial proteinases is under stringent control to prevent aberrant hydrolysis of structural proteins and disruption of tissue architecture. E-cadherin-dependent cell-cell adhesion is also important for maintenance of epithelial structural integrity, and loss of E-cadherin expression has been correlated with enhanced invasive potential in multiple tumor models. To address the hypothesis that there is a functional link between E-cadherin and proteinase expression, we have examined the role of E-cadherin in proteinase regulation. By using a calcium switch protocol to manipulate junction assembly, our data demonstrate that initiation of de novo E-cadherin-mediated adhesive contacts suppresses expression of both relative matrix metalloproteinase-9 levels and net urinary-type plasminogen activator activity. E-cadherin-mediated cell-cell adhesion increases both phosphatidylinositol 3'-kinase (PI3-kinase)-dependent AKT phosphorylation and epidermal growth factor receptor-dependent MAPK/ERK activation. Pharmacologic inhibition of the PI3-kinase pathway, but not the epidermal growth factor receptor/MAPK pathway, prevents E-cadherin-mediated suppression of proteinases and delays junction assembly. Moreover, inhibition of junction assembly with a function-blocking anti-E-cadherin antibody stimulates proteinase-dependent Matrigel invasion. As matrix metalloproteinase-9 and urinary-type plasminogen activator potentiate the invasive activity of oral squamous cell carcinoma, these data suggest E-cadherin-mediated signaling through PI3-kinase can regulate the invasive behavior of cells by modulating proteinase secretion.
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PMID:Proteinase suppression by E-cadherin-mediated cell-cell attachment in premalignant oral keratinocytes. 1213 62


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