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-derive d growth factor (PDGF) regulation of ornithine decarboxylase (ODC) expressi on during malignant conversion. H-ras-transformed cell lines exhibited PDGF -mediated alterations in ODC gene expression. These alterations involved tr anscriptional, 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 act ivity 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 alterati ons in ODC gene expression in C2 cells [capable of malignant progression (m etastasis formation)] were ras-dependent, required a tyrosine kinase activi ty, involved both MAP kinase-mediated events and phosphatidylinositol-3-kin ase (PI-3-kinase)-mediated events, and were dependent upon PTS G-protein-me diated signalling but independent of PKC-mediated events. PDGF-mediated reg ulation of ODC gene expression changes in response to H-ras-mediated cellul ar transformation and malignant progression. (C) 2001 Elsevier Science Inc. All rights reserved.