Platelet-derived growth factor mediated altered expression and regulation of ornithine decarboxylase in H-ras-transformed cell lines.
This study demonstrates a novel link between alterations in platelet-derived growth factor (PDGF) regulation of ornithine decarboxylase (ODC) expression during malignant conversion. H-ras-transformed cell lines exhibited PDGF-mediated alterations in ODC gene expression. These alterations involved transcriptional, posttranscriptional, and cycloheximide-mediated events. PDGF-mediated alterations in ODC gene expression in NR3 cells (capable of only benign tumour formation) were ras-dependent, involved a tyrosine kinase activity and mitogen-activated protein (MAP) kinase-mediated signalling events, and were independent of both protein kinase C (PKC) events and pertussis toxin-sensitive (PTS) G-protein-mediated signalling. PDGF-mediated alterations in ODC gene expression in C2 cells [capable of malignant progression (metastasis formation)] were ras-dependent, required a tyrosine kinase activity, involved both MAP kinase-mediated events and phosphatidylinositol-3-kinase (PI-3-kinase)-mediated events, and were dependent upon PTS G-protein-mediated signalling but independent of PKC-mediated events. PDGF-mediated regulation of ODC gene expression changes in response to H-ras-mediated cellular transformation and malignant progression.
Voskas
D
D
Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, 1-001, East Annex, 38 Shuter Street, M5B 1A6, Toronto, Ontario, Canada.
Kim
M
M
Hurta
R A
RA
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002461:Cell Line, Transformed; D003513:Cycloheximide / Q000494:pharmacology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000737:chemistry; D037342:Pertussis Toxin; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D003513:Cycloheximide; D037342:Pertussis Toxin; D011493:Protein Kinase C; D016283:Proto-Oncogene Proteins p21(ras); D009955:Ornithine Decarboxylase