Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.
AUTOR(ES)
Shaw, P
RESUMO
A wild-type p53 gene under control of the metallothionein MT-1 promoter was stably transfected into human colon tumor-derived cell line EB. Repeated inductions of the metallothionein wild-type p53 gene with zinc chloride results in progressive detachment of wild-type p53 cells grown on culture dishes. Examination at both the light and electron microscopic level revealed that cells expressing wild-type p53 developed morphological features of apoptosis. DNA from both attached and detached cells was degraded into a ladder of nucleosomal-sized fragments. Expression of wild-type p53 inhibited colony formation in soft agar and tumor formation in nude mice. Furthermore, established tumors in nude mice underwent regression if wild-type p53 expression was subsequently induced. Regressing tumors showed histological features of apoptosis. Thus, regression of these tumors was the result of apoptosis occurring in vivo. Apoptosis may be a normal part of the terminal differentiation program of colonic epithelial cells. Our results suggest that wild-type p53 could play a critical role in this process.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=49109Documentos Relacionados
- Introduction of wild-type p53 in a human ovarian cancer cell line not expressing endogenous p53.
- Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53
- Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins
- Induction of wild-type p53 activity in human cancer cells by ribozymes that repair mutant p53 transcripts
- p73 Function Is Inhibited by Tumor-Derived p53 Mutants in Mammalian Cells