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

Activated ras oncogene transfection into suitable recipient cells has been shown to induce the metastatic phenotype (Thorgeirsson, et al., Mol. Cell. Biol., 5: 259-262, 1985). We have used this model system to study the correlation of basement membrane collagenolysis with metastatic propensity. The c-Ha-ras oncogene alone, or combined with v-myc, transfected into early passage rat embryo fibroblasts, induce these cells to secrete high levels of type IV collagenolytic metalloproteinase and to concomitantly exhibit a high incidence of spontaneous metastases in nude mice. Cotransfection of c-Ha-ras plus the adenovirus type 2 E1a gene yields cells which are highly tumorigenic but nonmetastatic and fail to produce type IV collagenase. This effect is due to a suppression of collagenase elaboration, not increased production of a collagenase inhibitor, and not decreased production of a collagenase activator. The characteristics of the collagenase are identical to tumor type IV collagenase described previously. The nonmetastatic cells which failed to produce type IV collagenase retain the ability to secrete high levels of plasminogen activator. Transfection with the protooncogenic forms of Ha-ras or mos, or spontaneous transformation of NIH 3T3 cells or chemical transformation of BALB 3T3 cells yields cells which fail to produce collagenase, are tumorigenic, but totally nonmetastatic. These data support a biochemical linkage of type IV collagenase expression with the metastatic phenotype in this rodent system.
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PMID:Secretion of type IV collagenolytic protease and metastatic phenotype: induction by transfection with c-Ha-ras but not c-Ha-ras plus Ad2-E1a. 302 10

We have examined the expression of the transformed phenotype in a series of clonal lines of NIH/3T3 cells transfected with the human c-Ha-rasVal 12 oncogene and the neomycin phosphotransferase gene. Cells from individual transformed foci were cloned and subjected to detailed analyses of the ras sequences. Three clones were found that expressed approximately one, 2-4, or 4-8 copies of the human c-ras oncogene, respectively. A fourth clone had multiple copies of the transfected sequences, and expressed abundant c-Ha-ras RNA. Analysis of the transformed phenotype of various clones indicated that cells expressing low levels of mutant c-Ha-ras had lost some of their extracellular fibronectin network, and were barely altered in their cytoskeleton. In contrast, cells expressing abundant c-Ha-ras had lost both their actin and fibronectin networks and showed an increase in plasminogen activator activity. Cells with amplified c-Ha-rasVal 12 grew better in low serum, formed large colonies in soft agar and showed enhanced activity of ornithine decarboxylase, the rate-controlling enzyme in polyamine biosynthesis. These results show that the dosage level of the mutant oncogene makes a significant contribution to the transformed phenotype of c-Ha-ras oncogene-transformed cells.
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PMID:Dose effects of transfected c-Ha-rasVal 12 oncogene in transformed cell clones. 380 52

We tested distinct variants of a human keratinocyte line (HaCaT) for the expression of tissue-type plasminogen activator (tPA)-specific mRNA, as well as cell surface-associated and secreted tPA. Cells of early passages (passage no. 22) only expressed urokinase plasminogen activator (uPA)- but not tPA-specific mRNA. Cells after prolonged culture (passage no. 44) expressed uPA- and tPA-specific mRNA, but did not release tPA in the extracellular space and did not display surface-associated tPA. HaCaT cells transformed with the c-Ha-ras oncogene (HaCaTras) showed both secreted and surface-associated tPA antigen. The secreted and the surface-associated plasminogen activator (PA)-activity of HaCaTras cells were in part inhibitable by anticatalytic anti-tPA antibodies, thus indicating that tPA contributes to extracellular and surface-associated plasminogen activation. Finally, we demonstrate that tPA secretion of HaCaT 44 cells can be induced by retinoic acid, most likely via interaction of retinoic acid with nuclear-associated retinoic acid-receptor(s).
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PMID:tPA of human keratinocytes: contribution to cell surface-associated plasminogen activation and upregulation by retinoic acid. 860 43