Oncogenic transformation increases the sensitivity for apoptosis induction by inhibitors of macromolecular synthesis.
Inhibition of RNA or protein synthesis causes apoptosis in fibroblasts. This points to the constitutive expression of a long-lived apoptosis machinery which is controlled by shortlived negative regulatory proteins, termed endogenous survival factors. The length of time between addition of the inhibitor of macromolecular synthesis and the onset of apoptosis can be used as an estimation of the effective survival factor concentration. Transformation of rat fibroblasts by a constitutively expressed src oncogene or an inducible ras oncogene increases the sensitivity for apoptosis induction by inhibitors of macromolecular synthesis, indicating that their endogenous survival factor pool has been decreased.
Hanusch
J
J
Abteilung Virologie, Institut fur Medizinische Mikrobiologie und Hygiene, Universitat Freiburg, Germany.
Schwieger
A
A
Sers
C
C
Schäfer
R
R
Bauer
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000473:pathology / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000648:ultrastructure; D003513:Cycloheximide / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D011905:Genes, ras; D016391:Genes, src; D020287:In Situ Nick-End Labeling; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D007700:Kinetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000502:physiology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D002843:Chromatin; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D016211:Transforming Growth Factor alpha; D007544:Isopropyl Thiogalactoside; D019328:Buthionine Sulfoximine; D003513:Cycloheximide