Characterization of c-myc-transformed rat fibroblasts resistant to apoptosis induced ny growth factor deprivation.
Under appropriate conditions (e.g., growth factor withdrawal), the deregulated expression of c-myc in rodent fibroblasts leads to substantial cell death due to apoptosis. To better understand this process, we selected for c-myc-transformed Rat1A fibroblasts that were resistant to growth factor deprivation-induced cell death. One clonal isolate exhibited prolonged survival in serum-free medium and displayed reduced levels of apoptosis-related DNA fragmentation. These cells were also resistant to induction of apoptosis by the protein kinase inhibitor staurosporine. They retained a transformed cell phenotype and expressed the proviral human c-myc allele in an unaltered fashion, strongly indicating that the mutation of a cellular gene other than c-myc accounts for the apoptosis-resistant phenotype. The results of somatic cell hybrid analysis of this cell line are consistent with a recessive mutation. Our findings suggest a novel mechanism for abrogation of apoptosis in neoplastic cells and provide a model system for the study of its role in tumorigenesis and resistance to antineoplastic therapy.
Dhanaraj
S N
SN
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, 07103-2714, USA.
Marcus
A M
AM
Korah
R M
RM
Iwata
K
K
Small
M B
MB
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D016259:Genes, myc; D006133:Growth Substances / Q000172:deficiency*; D006801:Humans; D010641:Phenotype; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D051381:Rats; D019311:Staurosporine; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000470:Alkaloids; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D006133:Growth Substances; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D019311:Staurosporine