Epidermal growth factor, like phorbol esters, induces plasminogen activator in HeLa cells

Lee, Lih-Syng; Weinstein, I. Bernard

doi:10.1038/274696a0

Cited by 122 publications

(50 citation statements)

References 13 publications

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“…Thus it is tempting to speculate that stimulation of the EGF receptor by ctTGF fulfils an essential function in the establishment of fibrosarcomas involving the v-abl oncogene, e.g. in angiogenesis (Folkman, 1985), by changes in extracellular matrix proteins (Chen et al, 1977;McCarthy et al, 1985;Skantze et al, 1985) or via stimulating the secretion of plasminogen activator (Lee and Weinstein, 1978) or other proteinases (Eaton and Baker, 1983). If aTGF acts by stimulating the kinase activity of the EGF receptor, one would predict the existence of certain phosphotyrosyl proteins in v-abl-transformed cells induced by aTGF.…”

Section: Resultsmentioning

confidence: 99%

Abelson transformed fibroblasts lacking the EGF receptor are not tumourigenic in nude mice.

Gebhardt¹,

Bell²,

Foulkes³

1986

The EMBO Journal

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Section: Resultsmentioning

confidence: 99%

Abelson transformed fibroblasts lacking the EGF receptor are not tumourigenic in nude mice.

Gebhardt¹,

Bell²,

Foulkes³

1986

The EMBO Journal

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“…In transformed cells many of the characteristics of transformation are exaggerated. These include altered cell morphology (2,3), increased uptake of small molecules (2)(3)(4), alterations of the cell membrane (4,5), increased prostaglandin and polyamine synthesis (6)(7)(8), enhanced DNA synthesis and cell division (3,(9)(10)(11), and increased production of plasminogen activator (11,12). Furthermore, in most models studied phorbol esters inhibit terminal differentiation (2,13).…”

Section: Introductionmentioning

confidence: 99%

Antagonism between Epidermal Growth Factor and Phorbol Ester Tumor Promoters in Human Breast Cancer Cells

Osborne¹,

Hamilton²,

Nover³

et al. 1981

J. Clin. Invest.

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“…Regulation of the plasminogen activator system involves modulation by cofactors and inhibitors as well as controlled synthesis of the key components. It is well documented that t-PA expression is influenced by a variety of exogenous factors such as hormones, growth factors, and cytokines (3)(4)(5)(6). Regulation by these factors appears to be receptor-mediated and is imposed at the transcriptional level (7)(8)(9)(10).…”

mentioning

confidence: 99%

Low Density Lipoprotein Receptor-related Protein Modulates the Expression of Tissue-type Plasminogen Activator in Human Colon Fibroblasts

Hardy

Feder

Wolfe

et al. 1997

Journal of Biological Chemistry

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Human colon fibroblasts (HCF) produce tissue-type plasminogen activator (t-PA) in culture, but after 24 -48 h, t-PA ceases to accumulate in the medium. Here, we report negative feedback regulation of t-PA expression, exerted by t-PA or complexes of t-PA with its physiological inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Inhibition of t-PA expression could be induced by addition of exogenous t-PA or t-PA⅐PAI-1 complexes and reversed by monoclonal antibody directed against the active site of t-PA. Analysis of metabolically radiolabeled protein and cellular mRNA showed that both t-PA protein and mRNA levels declined considerably after 24 h. When 125 I-labeled t-PA or t-PA⅐PAI-1 complexes were incubated with HCF, monensin-inhibitable endocytosis and catabolism were observed. The low density lipoprotein receptor-related protein (LRP) was found to be expressed by HCF and to mediate these events. Addition of the 39-kDa receptor-associated protein (RAP), an antagonist for ligand interactions with LRP, removed the block to t-PA expression and restored its accumulation in the medium. Moreover, RAP completely prevented the degradation of exogenous 125 I-labeled t-PA by HCF, suggesting that LRP is the endocytic receptor for t-PA in these cells. These results demonstrate that cellular modulation of t-PA expression in HCF involves LRP receptor-mediated clearance of t-PA. This LRP receptor-mediated event results in down-regulation of t-PA expression at the mRNA level.Fibrinolysis is a complex process that requires precise regulation in vivo to ensure that it is neither deficient nor excessive. The plasminogen activator system is critical for thrombolysis, as well as other physiological processes including cell migration and tissue remodeling (1, 2). Human tissue-type plasminogen activator (t-PA) 1 (M r 68,000), a key serine protease in this system, is of particular pharmacological interest because of its value in the treatment of thromboembolic disorders. Regulation of the plasminogen activator system involves modulation by cofactors and inhibitors as well as controlled synthesis of the key components. It is well documented that t-PA expression is influenced by a variety of exogenous factors such as hormones, growth factors, and cytokines (3-6). Regulation by these factors appears to be receptor-mediated and is imposed at the transcriptional level (7-10). However, information on the role of t-PA in the local regulation of its own biosynthesis, release, and clearance is limited. Kadouri and Bohak (11) suggested a negative feedback-type control for t-PA expression in human lung fibroblasts but did not identify the mechanism by which expression was regulated. Although t-PA has been reported to undergo receptor-mediated binding to a variety of cultured cells (12-15), the biological significance of this phenomenon remains uncertain. Reports on the internalization and lysosomal degradation of t-PA have been largely confined to studies on hepatocytes, which have a known clearance function (for reviews, see Refs. 16,17)....

show abstract

Epidermal growth factor, like phorbol esters, induces plasminogen activator in HeLa cells

Cited by 122 publications

References 13 publications

Abelson transformed fibroblasts lacking the EGF receptor are not tumourigenic in nude mice.

Abelson transformed fibroblasts lacking the EGF receptor are not tumourigenic in nude mice.

Antagonism between Epidermal Growth Factor and Phorbol Ester Tumor Promoters in Human Breast Cancer Cells

Low Density Lipoprotein Receptor-related Protein Modulates the Expression of Tissue-type Plasminogen Activator in Human Colon Fibroblasts

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