PMID- 15026551
OWN - NLM
STAT- MEDLINE
DCOM- 20041109
LR  - 20200930
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 3
IP  - 3
DP  - 2004 Mar
TI  - Acyclic retinoid activates retinoic acid receptor beta and induces 
      transcriptional activation of p21(CIP1) in HepG2 human hepatoma cells.
PG  - 309-16
AB  - Acyclic retinoid (ACR), a novel synthetic retinoid, has recently been 
      demonstrated by us to inhibit the in vitro growth of human hepatoma cells, and 
      this effect was associated with decreased expression of cell cycle-related 
      molecules. These results, taken together with previous in vitro and clinical 
      studies with ACR, suggest that this agent may be useful in the chemoprevention 
      and therapy of hepatoma and possibly other human malignancies. In the present 
      study, we further examined the molecular effects of ACR on the HepG2 human 
      hepatoma cell line, focusing on the expression of nuclear retinoid receptors and 
      the cell cycle inhibitor protein p21(CIP1). Reverse transcription-PCR assays and 
      Western blot analyses indicated that these cells express retinoic acid receptors 
      (RARs) alpha, beta, and gamma, retinoid X receptors (RXRs) alpha and beta, and 
      peroxisome proliferator-activated receptors (PPAR) gamma mRNA. Treatment with ACR 
      caused a rapid induction within 3 h of RARbeta mRNA and the related protein, but 
      there was no significant change in the levels of the mRNA or proteins for RARs 
      alpha and gamma, RXRs alpha and beta, and PPARgamma. There was also a rapid 
      increase in p21(CIP1) mRNA and protein in HepG2 cells treated with ACR, and this 
      induction occurred via a p53-independent mechanism. In transient transfection 
      reporter assays, we cotransfected the retinoic acid response 
      element-chloramphenicol acetyltransferase (CAT) reporter gene into HepG2 cells 
      together with a RARbeta expression vector. RARbeta expression markedly stimulated 
      CAT activity (up to about 4-fold) after the addition of ACR. However, CAT 
      activity in the presence of ACR was only about 2-fold higher than that in the 
      absence of ACR, when cells were cotransfected with RARs alpha and gamma or 
      RXRalpha. These findings suggest that the growth inhibitory effects of ACR are 
      mediated at least in part through RARbeta and that both RARbeta and p21(CIP1) 
      play critical roles in the molecular mechanisms of growth inhibition induced by 
      ACR.
FAU - Suzui, Masumi
AU  - Suzui M
AD  - Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, 
      Columbia University, New York, NY, USA.
FAU - Shimizu, Masahito
AU  - Shimizu M
FAU - Masuda, Muneyuki
AU  - Masuda M
FAU - Lim, Jin T E
AU  - Lim JT
FAU - Yoshimi, Naoki
AU  - Yoshimi N
FAU - Weinstein, I Bernard
AU  - Weinstein IB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (DNA Primers)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (retinoic acid receptor beta)
RN  - 5688UTC01R (Tretinoin)
RN  - 81485-25-8 (3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Nucleus/metabolism
MH  - Chloramphenicol O-Acetyltransferase/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/*metabolism
MH  - DNA Primers/chemistry
MH  - Genes, Reporter
MH  - Humans
MH  - Models, Chemical
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Retinoid X Receptors
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tretinoin/*analogs & derivatives/*metabolism/*pharmacology
MH  - Tumor Suppressor Protein p53/metabolism
EDAT- 2004/03/18 05:00
MHDA- 2004/11/13 09:00
CRDT- 2004/03/18 05:00
PHST- 2004/03/18 05:00 [pubmed]
PHST- 2004/11/13 09:00 [medline]
PHST- 2004/03/18 05:00 [entrez]
PST - ppublish
SO  - Mol Cancer Ther. 2004 Mar;3(3):309-16.