Paradoxical inhibition of c-myc-induced carcinogenesis by Bcl-2 in transgenic mice.
Here, we investigated changes in apoptosis during tumor progression by analyzing the effect of coexpressing various antiapoptotic genes on the multistage process of c-myc-induced hepatocarcinogenesis in transgenic mice. Whereas continuous c-myc gene overexpression in the liver led to cellular hepatocarcinoma, the coexpression of the bcl-2 gene inhibited the emergence of liver tumors, by inhibiting a pretumoral phase characterized by increased proliferation and apoptosis. This antioncogenic effect was specific to Bcl-2 and was not shared by other antiapoptotic genes such as bcl-xL and a dominant negative form of p53. Thus, we have shown that Bcl-2 can have a tumor suppressor effect in vivo on c-myc-induced hepatocarcinogenesis during the emergence of neoplastic foci.
de La Coste
A
A
Institut National de la Santé et de la Recherche, U129, ICGM, Université Paris V René Descartes, France.
Mignon
A
A
Fabre
M
M
Gilbert
E
E
Porteu
A
A
Van Dyke
T
T
Kahn
A
A
Perret
C
C
D000818:Animals; D017209:Apoptosis; D018450:Disease Progression; D019254:Genes, bcl-2; D016259:Genes, myc; D016158:Genes, p53; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011770:Pyruvate Kinase / Q000235:genetics; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D051020:bcl-X Protein; D011770:Pyruvate Kinase