Protein kinase C-induced stimulation or inhibition of cellular proliferation in a murine macrophage tumor cell line.
M5076, a tumorigenic murine macrophage cell line, demonstrates diverse proliferative responses to a panel of protein kinase C activators. Thus, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate and mezerein potently inhibit cellular proliferation (by greater than 90%), whereas the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol markedly stimulates proliferation of serum-starved, quiescent M5076 cells. Another DG analogue, 1,2-dioctanoyl-sn-glycerol, has no effect on growth. However, all of these agents induce expression of c-fos oncogene mRNA levels to a similar magnitude and activate protein kinase C as determined by Mr 80,000 phosphorylation. Levels of c-fos protein induced by these treatments were markedly different with the antiproliferative agents producing greater c-fos protein levels.
Goode
N T
NT
ICRF Laboratories, Lincoln's Inn Fields, London, United Kingdom.
Moore
J P
JP
Hart
I R
IR
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology*; D004224:Diterpenes; D005260:Female; D005989:Glycerides / Q000494:pharmacology*; D016403:Lymphoma, Large B-Cell, Diffuse; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D013729:Terpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D004075:Diglycerides; D004224:Diterpenes; D005989:Glycerides; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013729:Terpenes; C011309:mezerein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C