Regulation of c-jun by lung carcinogens in clara cells of hamsters

L. R. Dolan, S. E. Rutberg, S. Amin, M. Emura, U. Mohr, A. Kraft, Z. Ronai

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Abstract

In vitro differentiated hamster Clara cells were used to study the effects of lung carcinogens on the regulation of the c-jun oncogene. Northern blot analysis revealed a decrease in the expression of jun transcripts 24 h following the exposure of Clara cells to the direct acting forms of benzo[a]pyrene (BPDE*) or 5-methylchrysene (5MeCDE). To determine whether this decrease was mediated at the transcriptional level, we have used CAT reporter constructs driven by nested deletions of the 5' non-coding regulatory region of the c-jun oncogene. While BPDE was capable of activating certain regulatory domains of the c-jun promoter, this activation was not observed with either 5MeCDE or the less active lung carcinogens BADE or 6MeCDE. Analysis of enhancer elements identified the SP1 target site as a strong silencer after BPDE treatment While positive regulatory element(s) mediating activation of c-jun by BPDE were localized within the promoter region up to -1639, further upstream sequences reduced this transcriptional activation. Thus, when the complete promoter region, up to -4500, was tested, no transcriptional activation was noted following BPDE treatment These observations suggest that the regulation of c-jun in Clara cells exposed to potent lung carcinogens is mediated at the post-transcriptional level, possibly by reducing the stability and, in turn, the half life of c-jun mRNA. Overall, in contrast to the response of cjun to numerous carcinogens and stress inducing agents noted in various other cell systems, our findings suggest the existence of a tissue-specific regulatory response for c-jun.

Original languageEnglish (US)
Pages (from-to)2789-2793
Number of pages5
JournalCarcinogenesis
Volume15
Issue number12
DOIs
StatePublished - Dec 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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    Dolan, L. R., Rutberg, S. E., Amin, S., Emura, M., Mohr, U., Kraft, A., & Ronai, Z. (1994). Regulation of c-jun by lung carcinogens in clara cells of hamsters. Carcinogenesis, 15(12), 2789-2793. https://doi.org/10.1093/carcin/15.12.2789