Evidence that p53 and bcl-2 are regulators of a common cell death pathway important for in vivo lymphomagenesis.
Multistep lymphomagenesis involves the deregulation of oncogenes and inactivation of tumor suppressor genes resulting in altered rates of proliferation as well as apoptotic cell death in tumor cells. The contribution of bcl-2 and p53 to the regulation of cell death during lymphomagenesis is assessed using bcl-2-1g, p53 'knock-out' (p53 KO), and p53 KO/bcl-2 hybrid mice. PCR-SSCP and DNA sequence analysis demonstrated that p53 somatic mutations are uncommon in lymphomas arising in bcl-2-Ig transgenic mice. Reduction in tumor latency was not observed in p53 KO/bcl-2 hybrid mice compared to p53 KO mice. Furthermore, overexpressed bcl-2 suppressed wild-type p53 associated apoptosis following gamma-radiation. These findings indicate that bcl-2 and p53 serve a suppressor and effector function, respectively, of a common cell death pathway. These findings also suggest that p53 somatic mutations provide no selective advantage during in vivo multistep lymphomagenesis in the context of bcl-2 gene deregulation.
Marin
M C
MC
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Hsu
B
B
Meyn
R E
RE
Donehower
L A
LA
el-Naggar
A K
AK
McDonnell
T J
TJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D004249:DNA Damage / Q000235:genetics; D017931:DNA Primers; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53