Expression of wild-type p53 in human A673 cells suppresses tumorigenicity but not growth rate.
The p53 gene has been found to be mutated in many different kinds of human cancers. In a previous study, expression of exogenous wild-type p53 in human osteosarcoma cells by retrovirus-mediated gene transfer resulted in marked enlargement of cell size, reduced growth rate in culture and loss of tumorigenicity in nude mice. Here we examine the effects of expression of wild-type or mutated p53 on human peripheral neuroepithelioma (PNET) A673 cells; these cells contained apparently normal alleles of the p53 gene but did not express a detectable quantity of p53 protein. Various characteristics of the p53-expressing cells were examined including morphology, growth rate, soft-agar colony formation, and tumorigenicity in nude mice. In contrast to osteosarcoma Saos-2 cells, expression of wild-type or mutant p53 protein in A673 cells had no effect on morphology or growth characteristics. However, clones expressing wild-type p53 protein had reduced ability to form colonies in soft agar and tumors in nude mice. To substantiate the genotype of wild-type p53-expressing cells, the proviral p53-encoding DNA of one cell clone was amplified by the polymerase chain reaction and sequenced. We concluded that expression of a single allele of the wild-type p53 gene was sufficient to suppress PNET A673 tumorigenicity but had no detectable effect on growth rate in culture.
Center for Molecular Medicine, University of Texas Health Science Center, San Antonio 78245.
Y M
YM
Chen
P L
PL
Chen
N
N
Arnaiz
D
D
Goodrich
W H
WH
Lee
D000595:Amino Acid Sequence; D002455:Cell Division / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014162:Transfection / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000473:pathology