Frequency and mechanisms of factor independence in IL-3-dependent cell lines.
Interleukin-3 (IL-3) -dependent cell lines were tested for spontaneous mutation frequency with respect to two markers, growth factor-independent growth and 8-azaguanine-resistant growth. The mutation frequency for the growth factor-independent growth was approximately equal to that of 8-azaguanine-resistant growth. Investigation of the growth factor-independent phenotypes indicated that at least two different mechanisms for growth factor independence existed. One mechanisms was the activation of the IL-3 gene by mutation resulting in the constitutive expression of IL-3 and autocrine regulated growth. A second mechanisms results in IL-3-independent growth in a manner in which (1) constitutive tyrosine kinase activity was not seen and (2) c-myc transcription was constitutively activated. Interestingly, in these cells both the tyrosine phosphorylation and c-myc transcriptional pathways are still activatable following IL-3 stimulation. At present, the exact nature of the mutation that results in this phenotype is not known.
Isfort
R J
RJ
Human and Environmental Safety Division, Procter and Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45239-8707.
D000818:Animals; D001375:Azaguanine / Q000494:pharmacology*; D002460:Cell Line; D002874:Chromosome Mapping; D004262:DNA Restriction Enzymes; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression / Q000187:drug effects; D005787:Gene Frequency / Q000235:genetics* / Q000502:physiology; D005819:Genetic Markers; D006133:Growth Substances / Q000502:physiology*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000032:analysis; D015151:Immunoblotting; D007377:Interleukin-3 / Q000235:genetics* / Q000502:physiology; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc; D014158:Transcription, Genetic / Q000187:drug effects; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D005819:Genetic Markers; D006133:Growth Substances; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D014443:Tyrosine; D007041:Hypoxanthine Phosphoribosyltransferase; D004262:DNA Restriction Enzymes; D001375:Azaguanine