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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 1994
Externally publishedYes

Fingerprint

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Carcinogens
Lung
Cricetinae
Activation
Chemical activation
Promoter
jun Genes
Cell
Genetic Promoter Regions
Transcriptional Activation
Decrease
Pyrene
Chemical elements
Messenger RNA
Deletion
Nucleic Acid Regulatory Sequences
Benzo(a)pyrene
Northern Blotting
Half-Life

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience
  • Cancer Research

Cite this

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

Regulation of c-jun by lung carcinogens in clara cells of hamsters. / Dolan, L. R.; Rutberg, S. E.; Amin, S.; Emura, M.; Mohr, U.; Kraft, Andrew; Ronai, Z.

In: Carcinogenesis, Vol. 15, No. 12, 12.1994, p. 2789-2793.

Research output: Contribution to journalArticle

Dolan, LR, Rutberg, SE, Amin, S, Emura, M, Mohr, U, Kraft, A & Ronai, Z 1994, 'Regulation of c-jun by lung carcinogens in clara cells of hamsters', Carcinogenesis, vol. 15, no. 12, pp. 2789-2793. https://doi.org/10.1093/carcin/15.12.2789
Dolan, L. R. ; Rutberg, S. E. ; Amin, S. ; Emura, M. ; Mohr, U. ; Kraft, Andrew ; Ronai, Z. / Regulation of c-jun by lung carcinogens in clara cells of hamsters. In: Carcinogenesis. 1994 ; Vol. 15, No. 12. pp. 2789-2793.
@article{5c409da937b44b0c8af850bfc69dd458,
title = "Regulation of c-jun by lung carcinogens in clara cells of hamsters",
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.",
author = "Dolan, {L. R.} and Rutberg, {S. E.} and S. Amin and M. Emura and U. Mohr and Andrew Kraft and Z. Ronai",
year = "1994",
month = "12",
doi = "10.1093/carcin/15.12.2789",
language = "English (US)",
volume = "15",
pages = "2789--2793",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Regulation of c-jun by lung carcinogens in clara cells of hamsters

AU - Dolan, L. R.

AU - Rutberg, S. E.

AU - Amin, S.

AU - Emura, M.

AU - Mohr, U.

AU - Kraft, Andrew

AU - Ronai, Z.

PY - 1994/12

Y1 - 1994/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028559866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028559866&partnerID=8YFLogxK

U2 - 10.1093/carcin/15.12.2789

DO - 10.1093/carcin/15.12.2789

M3 - Article

VL - 15

SP - 2789

EP - 2793

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 12

ER -