PMID- 9270011
OWN - NLM
STAT- MEDLINE
DCOM- 19970909
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 57
IP  - 16
DP  - 1997 Aug 15
TI  - Retinyl methyl ether down-regulates activator protein 1 transcriptional 
      activation in breast cancer cells.
PG  - 3444-50
AB  - Retinyl methyl ether (RME) is known to prevent the development of mammary cancer. 
      However, the mechanism by which RME exerts its anticancer effect is presently 
      unclear. The diverse biological functions of retinoids, the vitamin A 
      derivatives, are mainly mediated by their nuclear receptors, retinoic acid 
      receptors (RARs) and retinoid X receptors (RXRs). RARs and RXRs are 
      ligand-dependent transcriptional factors that either activate gene transcription 
      through their binding to retinoic acid response elements or repress 
      transactivation of genes containing the activator protein 1 (AP-1) binding site. 
      Previous studies demonstrated that RME can modulate transcriptional activity of 
      retinoid receptors on retinoic acid response elements, suggesting that regulation 
      of retinoid receptor activity may mediate the anticancer effect of RME. In this 
      study, we present evidence that RME can down-regulate AP-1 activity induced by 
      the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, insulin, growth factors, 
      and the nuclear proto-oncogenes c-Jun and c-Fos. Transient transfection assays 
      demonstrate that inhibition of AP-1 activity occurs on the human collagenase 
      promoter containing an AP-1 binding site or the thymidine kinase promoter linked 
      with an AP-1 binding site. In HeLa cells, the inhibition is observed when 
      RAR-alpha and/or RXR-alpha but not RAR-beta or RAR-gamma expression vectors are 
      cotransfected, whereas the endogenous retinoid receptors in breast cancer cells 
      T-47D and ZR-75-1 were sufficient to confer the inhibition by RME. Furthermore, 
      using gel retardation assay, we show that 12-O-tetradecanoylphorbol-13-acetate- 
      and epidermal growth factor-induced AP-1 binding activity in breast cancer cells 
      is inhibited by RME. These results suggest that one of the mechanisms by which 
      RME prevents cancer development may be due to the repression of AP-1-responsive 
      genes.
FAU - Agadir, A
AU  - Agadir A
AD  - The Burnham Institute, La Jolla Cancer Research Center, California 92037, USA.
FAU - Shealy, Y F
AU  - Shealy YF
FAU - Hill, D L
AU  - Hill DL
FAU - Zhang, X
AU  - Zhang X
LA  - eng
GR  - R01 CA60988/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Carcinogens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 11103-57-4 (Vitamin A)
RN  - 32450-56-9 (retinyl methyl ether)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 3.4.24.- (Collagenases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Carcinogens/antagonists & inhibitors
MH  - Collagenases/drug effects/metabolism
MH  - DNA-Binding Proteins/drug effects/metabolism
MH  - *Down-Regulation
MH  - Enzyme Activation/drug effects
MH  - Epidermal Growth Factor/pharmacology
MH  - Genes, Reporter/drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Proto-Oncogene Proteins c-fos/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-jun/antagonists & inhibitors/metabolism
MH  - Receptors, Retinoic Acid/*drug effects/genetics/metabolism
MH  - Retinoid X Receptors
MH  - Tetradecanoylphorbol Acetate/antagonists & inhibitors
MH  - Transcription Factor AP-1/*drug effects/genetics/metabolism
MH  - Transcription Factors/drug effects/genetics/metabolism
MH  - Transcriptional Activation/*drug effects
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Vitamin A/*analogs & derivatives/pharmacology
EDAT- 1997/08/15 00:00
MHDA- 1997/08/15 00:01
CRDT- 1997/08/15 00:00
PHST- 1997/08/15 00:00 [pubmed]
PHST- 1997/08/15 00:01 [medline]
PHST- 1997/08/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1997 Aug 15;57(16):3444-50.