Cited by 133Protein Kinase Regulation and GTPase SignalingCancer Genomics and DiagnosticsLung Cancer Treatments and Mutations

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Isolation of transforming sequences of two human lung carcinomas: structural and functional analysis of the activated c-K-ras oncogenes.

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Nakano, H, Yamamoto, F, Neville, C, Evans, D, Mizuno, T, Perucho, M·1984·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.81.1.71PMC PMC344612

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Abstract

Human lung tumors PR310 and PR371 maintained in nude mice contain activated c-K-ras oncogenes detectable by the ability of their DNAs to induce the morphological transformation of NIH 3T3 mouse fibroblasts. Using phage libraries constructed with DNA from NIH 3T3 mouse fibroblast transformants, we have isolated human sequences that span greater than 40 kilobase pairs of the c-K-ras oncogene. Based on the conservation of these human sequences in mouse fibroblast transformants, we conclude that the transforming ability of the oncogene activated in these tumors resides within a 43- to 46-kilobase-pair DNA region. No clear differences were observed between the structures of the PR310 and PR371 cloned oncogene sequences. Nucleotide sequence analysis in concert with DNA transfection experiments suggests that the PR371 oncogene has been activated by a single base change in the first exon, which results in the substitution of cysteine for glycine in position 12 of the predicted amino acid sequence. The genetic alteration responsible for the transforming activity of the PR310 oncogene, however, does not reside in the first exon. These results indicate that the activation of the c-K-ras oncogene in human lung cancer can occur by different mutational events.

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Authors: Nakano, H., Yamamoto, F., Neville, C., Evans, D., Mizuno, T., & Perucho, M.
Affiliations: Stony Brook University (US)
ORCID: Nakano, H
Yamamoto, F
Neville, C
Mizuno, T
Perucho, M
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1984-01
Volume: 81
Issue: 1
Pages: 71-75
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.81.1.71
PMC: PMC344612
OpenAlex: W1986093376
Cited by: 133
References: 30
Citations by year: 2023: 3 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 3 · 2012: 1
FWCI: 9.11
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords: oncogene activation, lung cancer, point mutations, cysteine substitution, oncogene structure, nude mouse xenograft, mutational mechanisms
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cell Transformation, Neoplastic, Chimera, Cloning, Molecular, DNA Restriction Enzymes, DNA, Neoplasm, Humans, Lung Neoplasms, Mice, Nude, Neoplasm Transplantation, Nucleic Acid Hybridization, Oncogenes, Transplantation, Heterologous, Mice

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Isolation of transforming sequences of two human lung carcinomas: structural and functional analysis of the activated c-K-ras oncogenes.

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