T Rytömaa1,2, K Grip-Rytömaa2. 1. Finnish Medical Society Duodecim, Helsinki, Finland. 2. Finnish Society of Radiobiology, Helsinki, Finland.
Abstract
OBJECTIVES: When rat chloroleukaemia (CHL) cells are grown undisturbed in a confined space, a genomic long interspersed nuclear element (LINE) is transcriptionally activated at a relatively low population density, followed by the retrotransposition of LINE and population death. This death programme is fundamentally different from conventional cell death pathways. MATERIALS AND METHODS: This work is essentially based on the re-analysis of relevant, old experimental data. Elemental analysis of a highly purified, long-stored inhibitor sample was performed. Genomic sequence searches were performed using the basic local alignment search tool (BLAST). RESULTS: This death programme is initiated by an endogenous inhibitor secreted by CHL cells. The inhibitor is almost certainly identical to the pentapeptide pyroGlu-Glu-Asp-Cys-Lys, shown to be a cell line-specific inhibitor of normal granulocytic cells. The inhibitor is derived from a highly conserved short open reading frame in mammalian genomes. CONCLUSIONS: Although spontaneous population death may be a biological oddity restricted to rat CHL cells, we suggest that this death programme is responsible for the eradication of cancer cells following treatment with an inhibitor administered exogenously.
OBJECTIVES: When rat chloroleukaemia (CHL) cells are grown undisturbed in a confined space, a genomic long interspersed nuclear element (LINE) is transcriptionally activated at a relatively low population density, followed by the retrotransposition of LINE and population death. This death programme is fundamentally different from conventional cell death pathways. MATERIALS AND METHODS: This work is essentially based on the re-analysis of relevant, old experimental data. Elemental analysis of a highly purified, long-stored inhibitor sample was performed. Genomic sequence searches were performed using the basic local alignment search tool (BLAST). RESULTS: This death programme is initiated by an endogenous inhibitor secreted by CHL cells. The inhibitor is almost certainly identical to the pentapeptide pyroGlu-Glu-Asp-Cys-Lys, shown to be a cell line-specific inhibitor of normal granulocytic cells. The inhibitor is derived from a highly conserved short open reading frame in mammalian genomes. CONCLUSIONS: Although spontaneous population death may be a biological oddity restricted to rat CHL cells, we suggest that this death programme is responsible for the eradication of cancer cells following treatment with an inhibitor administered exogenously.
Authors: Sarah A Slavoff; Andrew J Mitchell; Adam G Schwaid; Moran N Cabili; Jiao Ma; Joshua Z Levin; Amir D Karger; Bogdan A Budnik; John L Rinn; Alan Saghatelian Journal: Nat Chem Biol Date: 2012-11-18 Impact factor: 15.040