Coordinate N-ras mRNA up-regulation with mutational activation in tumorigenic guinea pig cells.

Nucleic acids research ·Vol. 16 ·No. 3 ·1988-02-11 ·Pages 969-80

Doniger J, DiPaolo JA

Abstract

Tumorigenic guinea pig cell lines with mutationally activated N-ras alleles also exhibited up-regulated N-ras mRNA. Mutational activation and mRNA up-regulation were limited to tumorigenic cells; preneoplastic progenitors were unaffected. Therefore, up-regulation occurred at a late stage of carcinogenesis closely associated with acquisition of tumorigenicity. cDNA and S1 protection analysis demonstrated that polyadenylation site of the short N-ras message and the mRNA start sites were different from that reported for human. The promoter region contained no canonical TATA or CCAAT boxes, but exhibited GGGCGG and CCGCCC SPl binding motifs characteristic of growth control genes. Moreover, both mutant and wild-type alleles were up-regulated in a guinea pig line heterozygous for N-ras codon 61. Coordinate N-ras mutational activation and up-regulation in five independent tumorigenic lines with unique chromosome constitutions suggests that both events are required for expression of the neoplastic phenotype.

MeSH Terms

Alleles Animals Cell Line Cell Transformation, Neoplastic/genetics DNA/genetics DNA, Recombinant Gene Expression Regulation Guinea Pigs Mutation Neoplasm Proteins/genetics Promoter Regions, Genetic Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins p21(ras) RNA, Messenger/biosynthesis RNA, Neoplasm/biosynthesis Tumor Cells, Cultured/metabolism

Chemicals

DNA, Recombinant Neoplasm Proteins Proto-Oncogene Proteins RNA, Messenger RNA, Neoplasm DNA Proto-Oncogene Proteins p21(ras)

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Doniger J

Laboratory of Biology, National Cancer Institute, Bethesda, MD 20892.

DiPaolo J A

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Article Info

Journal

Nucleic acids research

Abbr.

Nucleic Acids Res

ISSN

0305-1048

DOI

10.1093/nar/16.3.969

Published

1988-02-11

Pages

969-80

Language

English

Region

England

NLM ID

0411011

PMCID

PMC334731

Subset

External Links

PubMed source DOI: 10.1093/nar/16.3.969 PMC Full Text View journal details

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Coordinate N-ras mRNA up-regulation with mutational activation in tumorigenic guinea pig cells.

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