| Autor: |
Dhanaraj, Sridevi N., Marcus, Alexander M., Korah, Reju M., Iwata, Koichi, Small, Michael B. |
| Zdroj: |
Experimental Cell Research; April 1996, Vol. 224 Issue: 1 p52-62, 11p |
| Abstrakt: |
Under appropriate conditions (e.g., growth factor withdrawal), the deregulated expression of c-mycin 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-mycallele in an unaltered fashion, strongly indicating that the mutation of a cellular gene other than c-mycaccounts 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. |
| Databáze: |
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