Abstract |
Codon 248 in domain iv of the highly conserved region of the p53 gene is a frequent site of mutations associated with sporadic cancers and the familial cancer syndrome ( Li-Fraumeni syndrome). Therefore, a characterization of the functional significance of a codon 248 mutation is of interest. We used antisense RNA methodology to study the role of the wild-type and mutated p53 gene in cell growth and tumorigenesis. We introduced wild-type p53 complementary DNA in sense or antisense orientation under control of a beta-actin promoter into human non-small cell lung cancer cell line H322a which has a codon 248 mutation (G to T) and WTH226b which has wild type p53. The biological properties and p53 expression of stable G418-resistant clones were analyzed. We observed that in both cell lines antisense RNA expression significantly reduced p53 mRNA and protein production; it also caused increases in growth rate in cell cultures and in tumorigenicity in nu/nu mice for both cell types, suggesting that the mechanism by which p53 suppresses cell proliferation and tumorigenesis is not always abrogated by a codon 248 mutation.
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Authors | T Mukhopadhyay, J A Roth |
Journal | Cancer research
(Cancer Res)
Vol. 53
Issue 18
Pg. 4362-6
(Sep 15 1993)
ISSN: 0008-5472 [Print] United States |
PMID | 8364931
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
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Topics |
- Animals
- Base Sequence
- Cell Division
- Codon
- Genes, p53
- Humans
- Mice
- Molecular Sequence Data
- Mutation
- Neoplasms, Experimental
(pathology)
- RNA, Antisense
(pharmacology)
- Tumor Cells, Cultured
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