Melittin resistance: a counterselection for ras transformation.
The prevalence of activated ras oncogenes in human primary tumors suggests a central role for this oncogene in human cancer. Despite its ubiquitous distribution, the biochemical role of the oncogene remains unclear, and hence attempts to control its activity have been frustrated. This study demonstrates the ability of melittin, a 26 amino acid, amphipathic peptide from bee venom, to specifically select against cells in culture that express high levels of the ras oncogene. Acquisition of resistance to increasing concentrations of melittin is accompanied by corresponding decreases in the levels of expression of the ras oncoprotein and the number of copies of the ras gene. This results in a concomitant reversion of transformed cells to a normal morphology in a strict dose-dependent manner. Melittin is a known activator of cellular phospholipase A2 (PLA2), and these results suggest an interrelationship between ras and PLA2. In addition these studies indicate that melittin preferentially hyperactivates PLA2 in ras oncogene-transformed cells, resulting in their selective destruction.
Sharma
S V
SV
Department of Microbiology and Immunology, University of Tennessee, Memphis 38163.
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D011905:Genes, ras; D008555:Melitten / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2
D008555:Melitten; D010741:Phospholipases A; D054467:Phospholipases A2; D015689:Oncogene Protein p21(ras)