Suppression of lung cancer cell growth by ribozyme-mediated modification of p53 pre-mRNA.

D. W. Cai, T. Mukhopadhyay, Jack A Roth

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

An anti-p53 ribozyme (catalytic RNA) designed to cleave the p53 pre-messenger RNA (mRNA) can efficiently reduce the level of endogenous mutant p53 mRNA. Retrovirus-mediated transduction of a hammerhead ribozyme (Rz5a) designed to cleave unspliced p53 RNA at codon 187 near the boundary of intron 5 and exon 6 reduced the level of mutant p53 RNA and protein in the human H226Br lung cancer cell line, which contains a homozygous p53 mutation at codon 254. The catalytic cleavage of the p53 pre-mRNA but not the p53 mRNA by the ribozyme was shown in vitro. The cleavage of the p53 pre-mRNA by this ribozyme was specific because a mutation in its catalytic domain (Rz5m) abolished the cleavage activity in vitro. Expression of the Rz5a ribozyme significantly suppressed the growth of the H226Br cells in culture. However, another ribozyme (Rz7a) targeted at codon 264 of the p53 gene near the boundary of intron 7 and exon 8 showed in vitro cleavage of the pre-mRNA but did not suppress cell growth. The site of modification in the p53 pre-mRNA may determine the degree of ribozyme-mediated growth suppression in this cell line. Our findings that p53 pre-mRNA can be modified by a specific ribozyme in vivo suggest a possible role for these agents in gene therapy strategies for cancer.

Original languageEnglish (US)
Pages (from-to)199-205
Number of pages7
JournalCancer Gene Therapy
Volume2
Issue number3
StatePublished - Jan 1 1995

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Catalytic RNA
Lung Neoplasms
Messenger RNA
Growth
Codon
Introns
Exons
RNA
Cell Line
Mutation
p53 Genes
Retroviridae
Genetic Therapy
Catalytic Domain
Cell Culture Techniques

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Suppression of lung cancer cell growth by ribozyme-mediated modification of p53 pre-mRNA. / Cai, D. W.; Mukhopadhyay, T.; Roth, Jack A.

In: Cancer Gene Therapy, Vol. 2, No. 3, 01.01.1995, p. 199-205.

Research output: Contribution to journalArticle

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