Expression of p53 in Saos-2 osteosarcoma cells induces apoptosis which can be inhibited by Bcl-2 or the adenovirus E1B-55 kDa protein.
Studies were carried out to determine the effects of introducing p53 using an adenovirus gene transfer vector into p53 null human Saos-2 osteogenic carcinoma cells. Expression of p53 led to cell death within 30-40 h. The morphology of these cells as determined by electron microscopy indicated that death was by apoptosis. Such death was significantly reduced in Saos-2 variants that express high levels of the Bcl-2 suppressor of apoptosis. It was also found that the E1B-55 kDa protein of human adenovirus type 5, which was known to bind and inactivate p53, blocks Saos-2 cell death following expression of p53. These results thus directly demonstrate that this viral protein is able to inhibit p53-induced apoptosis.
Marcellus
R C
RC
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Teodoro
J G
JG
Charbonneau
R
R
Shore
G C
GC
Branton
P E
PE
D017501:Adenovirus E1B Proteins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008854:Microscopy, Electron; D012516:Osteosarcoma; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D017501:Adenovirus E1B Proteins; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53