PMID- 12939463
OWN - NLM
STAT- MEDLINE
DCOM- 20040621
LR  - 20200930
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 2
IP  - 8
DP  - 2003 Aug
TI  - Combination treatment with 1alpha,25-dihydroxyvitamin D3 and 9-cis-retinoic acid 
      directly inhibits human telomerase reverse transcriptase transcription in 
      prostate cancer cells.
PG  - 739-46
AB  - The vitamin D(3) receptor, which is the nuclear receptor for 
      1alpha,25-dihydroxyvitamin D(3) (VD(3)), forms a heterodimer with the retinoid X 
      receptor (RXR), which is the nuclear receptor for 9-cis-retinoic acid (9-cis-RA). 
      The heterodimer binds to a specific response element consisting of two directly 
      repeated pairs of motifs, AGGTGA, spaced by three nucleotides [direct repeat (DR) 
      3] and modulates the expression of VD(3)-responsive genes. Telomerase activity, 
      which is seen in most immortal cells and germ cells, is a complex of enzymes that 
      maintain the length of telomeres. One of the major components of human 
      telomerase, human telomerase reverse transcriptase (hTERT), is the catalytic 
      subunit, and the expression of hTERT might correlate most strongly with 
      telomerase activity. We found that the sequence of 5'-AGTTCATGGAGTTCA-3' (DR3') 
      is similar to that of DR3 in the promoter region of hTERT. Our results showed 
      that the combination of VD(3) and 9-cis-RA inhibited telomerase activity through 
      direct interaction of the heterodimer of vitamin D(3) receptor and RXR with the 
      DR3' sequence in the hTERT promoter as well as the combination of VD(3) and 
      selective RXR ligand did. Also, in vivo data showed that the growth of xenografts 
      in nude mice was inhibited by VD(3) and 9-cis-RA. The results of the present 
      study provide evidence on the molecular mechanism of the inhibition of cell 
      growth by these agents, and they could be novel therapeutic agents for prostate 
      cancer.
FAU - Ikeda, Naoya
AU  - Ikeda N
AD  - Department of Urology, Graduate School of Medicine, Yokohama City University, 
      Kanagawa 236-0004, Japan.
FAU - Uemura, Hiroji
AU  - Uemura H
FAU - Ishiguro, Hitoshi
AU  - Ishiguro H
FAU - Hori, Mayumi
AU  - Hori M
FAU - Hosaka, Masahiko
AU  - Hosaka M
FAU - Kyo, Satoru
AU  - Kyo S
FAU - Miyamoto, Ken-ichi
AU  - Miyamoto K
FAU - Takeda, Eiji
AU  - Takeda E
FAU - Kubota, Yoshinobu
AU  - Kubota Y
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.7.49 (Telomerase)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Alitretinoin
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Calcitriol/*pharmacology
MH  - DNA-Binding Proteins
MH  - Drug Synergism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Promoter Regions, Genetic/drug effects
MH  - Prostatic Neoplasms/drug therapy/enzymology/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Telomerase/antagonists & inhibitors/genetics/*metabolism
MH  - Transcription, Genetic/drug effects
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2003/08/27 05:00
MHDA- 2004/06/24 05:00
CRDT- 2003/08/27 05:00
PHST- 2003/08/27 05:00 [pubmed]
PHST- 2004/06/24 05:00 [medline]
PHST- 2003/08/27 05:00 [entrez]
PST - ppublish
SO  - Mol Cancer Ther. 2003 Aug;2(8):739-46.