title: A codon 248 p53 mutation retains tumor suppressor function as shown by enhancement of tumor growth by antisense p53.
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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
authors.forename: T
authors.initials: T
authors.lastname: Mukhopadhyay
authors.forename: J A
authors.initials: JA
authors.lastname: Roth
mesh_terms: D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D003062:Codon; D016158:Genes, p53; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009374:Neoplasms, Experimental / Q000473:pathology*; D016372:RNA, Antisense / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D003062:Codon; D016372:RNA, Antisense