PMID- 9507016
OWN - NLM
STAT- MEDLINE
DCOM- 19980416
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 12
DP  - 1998 Mar 20
TI  - All-trans-retinoic acid inhibits Jun N-terminal kinase-dependent signaling 
      pathways.
PG  - 7066-71
AB  - Retinoids, including retinol and retinoic acid derivatives, inhibit the growth of 
      normal human bronchial epithelial (HBE) cells. The signaling pathways through 
      which retinoids mediate this effect have not been defined. Normal HBE cell growth 
      is stimulated by treatment with a variety of growth factors that increase 
      mitogen-activated protein (MAP) activity. In this study, we examined MAP 
      kinase-dependent pathways as potential targets of retinoid signaling and the role 
      of MAP kinases in retinoid-induced c-fos gene regulation. All-trans-retinoic acid 
      (t-RA) inhibited Jun N-terminal kinase (JNK) and, to a lesser extent, 
      extracellular signal-regulated kinase activity in normal HBE cells. t-RA reduced 
      c-fos mRNA and protein levels by decreasing c-fos gene transcription. The c-fos 
      promoter was activated by co-transfection with a constitutively active JNK kinase 
      (SEK)-1 and suppressed by a dominant negative JNK kinase kinase (MEKK)-1. 
      Furthermore, c-fos expression was inhibited by agonists of retinoic acid 
      receptors (RARs) or retinoid X receptors (RXRs), and suppression of c-fos 
      promoter activity by t-RA was abrogated by treatment with antagonists of 
      RAR-alpha or of all the RXRs. These findings provide the first evidence that t-RA 
      inhibits JNK activity and demonstrate a potential role of JNK-dependent pathways 
      in the suppression of c-fos expression by t-RA. Furthermore, c-fos expression was 
      inhibited through activation of RAR- and RXR-dependent signaling pathways. In 
      light of the growth activation induced by JNK/SEK-dependent pathways in a variety 
      of cells, these data support further investigation into the role of JNK-dependent 
      signaling in the growth-suppressive effects of retinoids.
FAU - Lee, H Y
AU  - Lee HY
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. 
      D. Anderson Cancer Center, Houston, Texas 77030, USA.
FAU - Walsh, G L
AU  - Walsh GL
FAU - Dawson, M I
AU  - Dawson MI
FAU - Hong, W K
AU  - Hong WK
FAU - Kurie, J M
AU  - Kurie JM
LA  - eng
GR  - P50 CA70907/CA/NCI NIH HHS/United States
GR  - R29 CA67353/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, Retinoic Acid)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Bronchi/cytology/drug effects/enzymology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cells, Cultured
MH  - Gene Expression Regulation/drug effects
MH  - Genes, fos
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - *Mitogen-Activated Protein Kinases
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Tretinoin/*pharmacology
EDAT- 1998/04/18 00:00
MHDA- 1998/04/18 00:01
CRDT- 1998/04/18 00:00
PHST- 1998/04/18 00:00 [pubmed]
PHST- 1998/04/18 00:01 [medline]
PHST- 1998/04/18 00:00 [entrez]
AID - S0021-9258(18)63987-0 [pii]
AID - 10.1074/jbc.273.12.7066 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Mar 20;273(12):7066-71. doi: 10.1074/jbc.273.12.7066.