Expression level of Bcl-2 determines anti- or proapoptotic function.
Bcl-2 is an oncogene with antiapoptotic function. However, Bcl-2 is converted to a Bax-like death effector by caspases, suggesting that the expression of Bcl-2 may not favor the growth of cancers. We introduced the Bcl-2 gene to gliomas via adenovirus (Adv; Adv-Bcl-2) with the Adv for Fas (Adv-Fas) and the Adv for Fas ligand (Adv-FL) to evaluate the antiapoptotic function of Bcl-2. In U251 glioblastoma cells, Bcl-2 at a low level of expression repressed apoptosis induced by Adv-Fas and Adv-FL, whereas Bcl-2 at a high level of expression did not. On the other hand, Bcl-X(L) showed antiapoptotic function against Fas-mediated apoptosis, irrespective of its expression level. In glioblastoma cells, induction of Bcl-2 alone at a high level induced apoptosis, whereas induction of Bcl-X(L) alone did not. As the multiplicity of infection of Adv-Bcl-2 was increased, the quantity of a cleaved product of Bcl-2 increased. Induction of caspase-inhibitory genes (CrmA and p35) inhibited apoptosis induced by Adv-Bcl-2. Induction of Bcl-2 led to alteration of the membrane potential and structure of the mitochondria. In summary, although Bcl-2 at a low level of expression was antiapoptotic, Bcl-2 at a high level of expression was proapoptotic to Fas-mediated apoptosis. Overexpression of Bcl-X(L) was consistently antiapoptotic to Fas-mediated apoptosis.
Shinoura
N
N
Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Yoshida
Y
Y
Nishimura
M
M
Muramatsu
Y
Y
Asai
A
A
Kirino
T
T
Hamada
H
H
D017209:Apoptosis / Q000235:genetics*; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor