Opposite role of Bax and BCL-2 in the anti-tumoral responses of the immune system.
BACKGROUND
The relative role of anti apoptotic (i.e. Bcl-2) or pro-apoptotic (e.g. Bax) proteins in tumor progression is still not completely understood.


METHODS
The rat glioma cell line A15A5 was stably transfected with human Bcl-2 and Bax transgenes and the viability of theses cell lines was analyzed in vitro and in vivo.


RESULTS
In vitro, the transfected cell lines (huBax A15A5 and huBcl-2 A15A5) exhibited different sensitivities toward apoptotic stimuli. huBax A15A5 cells were more sensitive and huBcl-2 A15A5 cells more resistant to apoptosis than mock-transfected A15A5 cells (pCMV A15A5). However, in vivo, in syngenic rat BDIX, these cell lines behaved differently, as no tumor growth was observed with huBax A15A5 cells while huBcl-2 A15A5 cells formed large tumors. The immune system appeared to be involved in the rejection of huBax A15A5 cells since i) huBax A15A5 cells were tumorogenic in nude mice, ii) an accumulation of CD8+ T-lymphocytes was observed at the site of injection of huBax A15A5 cells and iii) BDIX rats, which had received huBax A15A5 cells developed an immune protection against pCMV A15A5 and huBcl-2 A15A5 cells.


CONCLUSIONS
We show that the expression of Bax and Bcl-2 controls the sensitivity of the cancer cells toward the immune system. This sensitization is most likely to be due to an increase in immune induced cell death and/or the amplification of an anti tumour immune response
UMR 601 INSERM/UN, (Equipe 2), 9 quai Moncousu 44035 Nantes, France. bougras@nantes.inserm.fr
Gwenola
G
Bougras
Pierre-François
PF
Cartron
Fabien
F
Gautier
Stéphane
S
Martin
Marité
M
LeCabellec
Khaled
K
Meflah
Marc
M
Gregoire
François M
FM
Vallette
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D018450:Disease Progression; D005910:Glioma / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type / Q000032:analysis; D018655:Lymphocyte Count; D051379:Mice; D008819:Mice, Nude; D055651:NK Cell Lectin-Like Receptor Subfamily B; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D000954:Antigens, Surface; C494827:Bax protein, mouse; C494828:Bax protein, rat; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein