PMID- 9678718
OWN - NLM
STAT- MEDLINE
DCOM- 19980813
LR  - 20190826
IS  - 0145-2126 (Print)
IS  - 0145-2126 (Linking)
VI  - 22
IP  - 6
DP  - 1998 Jun
TI  - A novel retinoic acid receptor (RAR)-selective antagonist inhibits 
      differentiation and apoptosis of HL-60 cells: implications of RARalpha-mediated 
      signals in myeloid leukemic cells.
PG  - 517-25
AB  - Retinoic acid (RA) induces HL-60 cells to differentiate terminally into mature 
      granulocytes, which subsequently die by apoptosis. The biological effects of RA 
      are mediated by two distinct families of transcription factors: retinoic acid 
      receptors (RARs) and retinoid X receptors (RXRs). RARs and RXRs form heterodimers 
      and regulate retinoid-mediated gene expression. We have recently developed a 
      novel RAR-selective antagonist (ER27191) which prevents RAR activation by 
      retinoids. Using this RAR-selective antagonist, and RXR and RAR agonist, we 
      demonstrate the RAR-mediated signaling pathway is important for differentiation 
      and apoptosis of myeloid leukemic cells. Simple activation of RXRs is not 
      sufficient to induce apoptosis of the cells. Interestingly, the combination of 
      the RAR-selective antagonist and 9-cis RA resulted in partial differentiation and 
      apoptosis of HL-60 and NB4 cells, whereas the RAR antagonist completely blocked 
      all-trans RA-induced differentiation and apoptosis of the cells. Additional 
      experiments showed that levels of BCL-2 protein decreased during differentiation 
      of myeloid leukemic cells. Furthermore, HL-60 cells transduced with a bcl-2 
      expression vector showed the same differentiation response to retinoids as did 
      parental HL-60 cells even though apoptosis was inhibited in these 
      bcl-2-transduced cells, suggesting that differentiation and apoptosis are 
      regulated independently in myeloid leukemic cells.
FAU - Ueno, H
AU  - Ueno H
AD  - Division of Hematology, Keio University School of Medicine, Tokyo, Japan.
FAU - Kizaki, M
AU  - Kizaki M
FAU - Matsushita, H
AU  - Matsushita H
FAU - Muto, A
AU  - Muto A
FAU - Yamato, K
AU  - Yamato K
FAU - Nishihara, T
AU  - Nishihara T
FAU - Hida, T
AU  - Hida T
FAU - Yoshimura, H
AU  - Yoshimura H
FAU - Koeffler, H P
AU  - Koeffler HP
FAU - Ikeda, Y
AU  - Ikeda Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 
      (4-(4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)anthra-(1,2-b)pyrrol-3-yl)benzoic 
      acid)
RN  - 0 (Anthracenes)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Pyrroles)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Alitretinoin
MH  - Anthracenes/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Drug Resistance
MH  - HL-60 Cells/*cytology/*drug effects/*physiology
MH  - Humans
MH  - Leukemia, Myeloid/pathology
MH  - Leukocytes/physiology
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis/pharmacology
MH  - Pyrroles/*pharmacology
MH  - Receptors, Retinoic Acid/*antagonists & inhibitors/metabolism/physiology
MH  - Retinoic Acid Receptor alpha
MH  - Signal Transduction
MH  - Tretinoin/metabolism/pharmacology
EDAT- 1998/07/25 00:00
MHDA- 1998/07/25 00:01
CRDT- 1998/07/25 00:00
PHST- 1998/07/25 00:00 [pubmed]
PHST- 1998/07/25 00:01 [medline]
PHST- 1998/07/25 00:00 [entrez]
AID - S0145212698000265 [pii]
AID - 10.1016/s0145-2126(98)00026-5 [doi]
PST - ppublish
SO  - Leuk Res. 1998 Jun;22(6):517-25. doi: 10.1016/s0145-2126(98)00026-5.