Platelet-activating factor (PAF) induces growth stimulation, inhibition, and suppression of oncogenic transformation in NRK cells overexpressing the PAF receptor.
Platelet-activating factor (PAF) is a phospholipid mediator with various physiological functions, including cellular growth and transformation. PAF exerts biological activities through G-protein-coupled receptors. In normal rat fibroblasts overexpressing a cloned PAF receptor, PAF induced immediate early oncogene expression and mitogenic responses. On the other hand, PAF strongly inhibited the epidermal growth factor-induced mitogenic growth response, growth acceleration, and anchorage-independent cell growth in a soft agar. Furthermore, PAF suppressed v-src- or v-ras-induced oncogenic morphological changes and anchorage-independent growth. Our observations suggest that PAF is a unique growth regulator with apparently diverse functions. Dual actions of PAF may relate to the point of action in the cell cycle; PAF stimulates the mitogenic response in G0-arrested cells in a pertussis toxin-sensitive manner, while it inhibits the G1 to S transition through a pertussis toxin-resistant manner.
Kume
K
K
Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo, Tokyo 113, Japan. kkume@m.u-tokyo.ac.jp
Shimizu
T
T
D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019938:Cyclin D1; D016213:Cyclins / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D051381:Rats; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016213:Cyclins; D015513:Oncogene Proteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D010566:Virulence Factors, Bordetella; C039351:platelet activating factor receptor; D019938:Cyclin D1; D037342:Pertussis Toxin