scholarly journals Pleiotropic derepression of developmentally regulated cellular and viral genes by c-myc proto-oncogene products in undifferentiated embryonal carcinoma cells

1989 ◽  
Vol 17 (2) ◽  
pp. 735-753 ◽  
Author(s):  
R. Onclercq ◽  
A. Lavenu ◽  
C. Cremisi
Keyword(s):  
Embryonal Carcinoma ◽  
Carcinoma Cells ◽  
Embryonal Carcinoma Cells ◽  
Developmentally Regulated ◽  
Viral Genes ◽  
Oncogene Products

Expression of extracellular matrix-degrading metalloproteinases and metalloproteinase inhibitors is developmentally regulated during endoderm differentiation of embryonal carcinoma cells

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 211-220 ◽  
Author(s):  
R.R. Adler ◽  
C.A. Brenner ◽  
Z. Werb
Keyword(s):  
Extracellular Matrix ◽  
Embryonal Carcinoma ◽  
Embryoid Bodies ◽  
Carcinoma Cells ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Embryonal Carcinoma Cells ◽  
Developmentally Regulated ◽  
F9 Cells ◽  
Metalloproteinase Inhibitors ◽  
Parietal Endoderm

The differentiation of F9 and PSA-1 embryonal carcinoma cells to embryoid bodies composed of a mixture of parietal and visceral endoderm was accompanied by changes in their secretion of metalloproteinases. Differentiation was induced by retinoic acid and dibutyryl cyclic AMP (for F9 cells) or by removing cells from a substrate of feeder cells to alter cell-cell interaction and adhesion (for PSA-1 cells). The embryoid bodies attached to gelatin-coated dishes, and the parietal endoderm cells spread out over the matrix. The differentiated cells secreted specific gelatin- and casein-degrading proteinases, including enzymes that comigrated with proenzyme forms of collagenase and stromelysin. Total proteinase activity as well as specific collagenase activity increased with the time of differentiation. All of the gelatin- and casein-degrading proteinases detectable by substrate gel zymography were inhibited by inhibitors of metalloproteinases but not by inhibitors of serine or cysteine proteinases, indicating that they were metalloproteinases. Both cell lines showed increased collagenolytic activity, which was activated by treatment with plasmin. In addition, both cell lines showed increased secretion of specific metalloproteinase inhibitors, including tissue inhibitor of metalloproteinases, with differentiation. Analysis of mRNA from undifferentiated and differentiated F9 cells by RNA blot analysis or reverse transcription coupled with the polymerase chain reaction showed that increased expression of genes for collagenase, stromelysin and tissue inhibitor of metalloproteinases is associated with differentiation of these cells. These results suggest that the expression of extracellular matrix-degrading metalloproteinases and their inhibitors is developmentally regulated during the differentiation and spreading of the parietal endoderm.

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