Transforming growth factor-beta differently regulates urokinase type plasminogen activator and matrix metalloproteinase-9 expression in mouse macrophages; analysis of intracellular signal transduction

2015 ◽  
Vol 39 (5) ◽  
pp. 619-628 ◽  
Author(s):  
Sonja S. Mojsilović ◽  
Juan F. Santibanez
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Mouse Macrophages ◽  
Intracellular Signal ◽  
Growth Factor Beta ◽  
Metalloproteinase 9

scholarly journals Transforming Growth Factor-Beta and Urokinase-Type Plasminogen Activator: Dangerous Partners in Tumorigenesis—Implications in Skin Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-26 ◽  
Author(s):  
Juan F. Santibanez
Keyword(s):  
Growth Factor ◽  
Skin Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Upa System ◽  
Growth Factor Beta

Transforming growth factor-beta (TGF-β) is a pleiotropic factor, with several different roles in health and disease. TGF-β has been postulated as a dual factor in tumor progression, since it represses epithelial tumor development in early stages, whereas it stimulates tumor progression in advanced stages. During tumorigenesis, cancer cells acquire the capacity to migrate and invade surrounding tissues and to metastasize different organs. The urokinase-type plasminogen activator (uPA) system, comprising uPA, the uPA cell surface receptor, and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and regulates key cellular events by activating intracellular signal pathways, which together allow cancer cells to survive, thus, enhancing cell malignance during tumor progression. Due to their importance, uPA and its receptor are tightly transcriptionally regulated in normal development, but are deregulated in cancer, when their activity and expression are related to further development of cancer. TGF-β regulates uPA expression in cancer cells, while uPA, by plasminogen activation, may activate the secreted latent TGF-β, thus, producing a pernicious cycle which contributes to the enhancement of tumor progression. Here we review the specific roles and the interplay between TGF-β and uPA system in cancer cells and their implication in skin cancer.

Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation

1989 ◽  
Vol 9 (3) ◽  
pp. 1255-1262
Author(s):  
L Pertovaara ◽  
L Sistonen ◽  
T J Bos ◽  
P K Vogt ◽  
J Keski-Oja ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Base Line ◽  
Tgf Beta ◽  
Early Effect ◽  
Growth Factor Beta

Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta.

Transforming Growth Factor Beta Signal Transduction in the Kidney

1998 ◽  
Vol 21 (2-4) ◽  
pp. 259-261 ◽  
Author(s):  
Erwin P. Böttinger ◽  
Jiahong Miao ◽  
Mario Schiffer ◽  
Markus Bitzer ◽  
Ian S.D. Roberts
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta
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