Cooperative interaction between c-myc and bcl-2 proto-oncogenes.
The bcl-2 proto-oncogene is activated by translocation in a variety of B-lymphoid tumours and synergizes with the c-myc oncogene in tumour progression. The mechanism of synergy is unclear but bcl-2 expression inhibits apoptosis, a property presumably pertinent to its proto-oncogenic mode of action. We have shown that the c-myc gene is a potent inducer of apoptosis, in addition to its established role in mitogenesis. Here we show that expression of the bcl-2 protein, Bcl-2, specifically abrogates c-myc-induced apoptosis without affecting the c-myc mitogenic function. This provides a novel mechanism for oncogene cooperation, of potential importance both in carcinogenesis and in the evolution of drug resistance in tumours.
Fanidi
A
A
Biochemistry of the Cell Nucleus Laboratory, Imperial Cancer Research Fund, London, UK.
Harrington
E A
EA
Evan
G I
GI
D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D016259:Genes, myc / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008938:Mitosis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen / Q000235:genetics; D013997:Time Factors
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D004958:Estradiol