Deregulated expression of human c-jun transforms primary rat embryo cells in cooperation with an activated c-Ha-ras gene and transforms Rat-1a cells as a single gene

J. Schutte, J. D. Minna, M. J. Birrer

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

While the ability of the retroviral oncogene v-jun to transform chicken cells led to its discovery, the oncogenic potential of its cellular homologue, c-jun, which encodes a transcription factor, is unknown. We isolated a 1070-base-pair cDNA clone containing the unmutated entire open reading frame of c-jun from a human small cell lung cancer line. This cDNA as well as a 5.6-kilobase normal human genomic DNA fragment containing the c-jun gene were placed under the control of retroviral long terminal repeats and introduced into primary rat embryo cells (RECs), with or without other oncogenes, and into an immortal rat fibroblast cell line, Rat-1a, as a single gene. In Rat-1a cells the expression of human c-jun mRNA was associated with the ability to clone in soft agarose and form tumors in nude mice. When the c-jun cDNA or genomic DNA constructs were introduced into RECs, no foci of transformed cells were seen with c-jun alone or c-jun cotransfected with deregulated c-myc or L-myc protooncogenes. However, cotransfection of the c-jun constructs with an activated human c-Ha-ras gene led to foci of transformed cells which gave rise to immortalized cell lines that cloned in soft agarose and formed tumors in nude mice. Furthermore, formation of foci of transformed RECs by the c-jun/ras combination was augmented 3-fold by the tumor promoter phorbol 12-tetradecanoate 13-acetate. We conclude that deregulated expression of human c-jun can participate in malignant transformation of normal mammalian cells.

Original languageEnglish (US)
Pages (from-to)2257-2261
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number7
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • General

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