Negative cell cycle control of human T cells by beta-galactoside binding protein (beta GBP): induction of programmed cell death in leukaemic cells.
The cell cycle is negatively regulated by diverse molecular events which originate in part from the interaction of secreted proteins with specific cell surface receptors. By exerting negative control on cell proliferation, these factors can help maintain cell number balance both through growth restraints and the induction of apoptosis and may thus contribute to prevent or control tumourigenesis. Here we report that betaGBP, a negative growth factor which controls transition from S phase into G2, causes an S/G2 growth arrest in both normal and leukaemic T cells. However, in leukaemic T cells but not in normal T lymphocytes, growth arrest is followed by apoptosis. Analysis of possible mechanisms of induction of apoptosis does not support Fas and Fas L as having a main role but points instead to Bcl-2 and Bax. The induction of apoptosis in leukaemic T cells is characterised by the decrease of Bcl-2 and consequent predominance of Bax. By contrast, in the normal T cells, which do not enter apoptosis, the quantitative relationship of Bcl-2 to Bax remains unchanged. The ability of betaGBP to selectively induce apoptosis in leukaemic cells suggests that betaGBP may play a role in cancer surveillance and that its use has potential therapeutic implications.
Novelli
F
F
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Allione
A
A
Wells
V
V
Forni
G
G
Mallucci
L
L
D017209:Apoptosis / Q000187:drug effects*; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D037161:Galectins; D015972:Gene Expression Regulation, Neoplastic; D006388:Hemagglutinins / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
C494826:BAX protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D037161:Galectins; D006388:Hemagglutinins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D019014:fas Receptor