Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.
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.
Shaw
P
P
CHUV, Department of Virology, Lausanne, Switzerland.
Bovey
R
R
Tardy
S
S
Sahli
R
R
Sordat
B
B
Costa
J
J
D001483:Base Sequence; D016923:Cell Death / Q000235:genetics*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007700:Kinetics; D008668:Metallothionein / Q000235:genetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D008668:Metallothionein