PMID- 16732322
OWN - NLM
STAT- MEDLINE
DCOM- 20061213
LR  - 20181113
IS  - 0950-9232 (Print)
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 25
IP  - 53
DP  - 2006 Nov 9
TI  - Induction of kinase suppressor of RAS-1(KSR-1) gene by 1, 
      alpha25-dihydroxyvitamin D3 in human leukemia HL60 cells through a vitamin D 
      response element in the 5'-flanking region.
PG  - 7078-85
AB  - Differentiation therapy is being developed as an additional therapeutic option 
      for the treatment of several forms of cancer, including myeloid leukemia. In 
      model systems, the physiologically active form of vitamin D, 1, 
      alpha25-dihydroxyvitamin D3 (1,25D), induces monocytic differentiation of human 
      myeloid cells, but the mechanism is not clear. We report here, the first direct 
      connection between the signal provided by 1,25D and the molecular circuitry known 
      to be involved in monocytic differentiation. Specifically, we show that 1,25D 
      selectively increases the expression of the gene encoding kinase suppressor of 
      Ras-1 (KSR-1) in HL60 cells, while other differentiation-inducing agents such as 
      12-O-tetradecanoylphorbol-13-acetate, retinoic acid or dimethyl sulfoxide do not 
      significantly increase KSR-1 expression. Further, the upregulation of KSR-1 gene 
      by 1,25D is competed by ZK159222, an antagonist of vitamin D receptor (VDR) 
      action, and can occur in the presence of protein synthesis inhibitor 
      cycloheximide, showing that the effect is direct. Most importantly, we have 
      identified a vitamin D responsive element (VDRE) in the promoter region of the 
      human KSR-1 gene, to which VDR binds in a 1,25D-dependent manner, in vitro and in 
      vivo. This binding is paralleled by increased association of RNA polymerase II 
      with the transcription start site of KSR-1 gene, and the VDRE is functional in 
      reporter assays. Our findings offer a potential mechanism for a signaling pathway 
      that contributes to 1,25D-induced monocytic differentiation of human myeloid 
      leukemia cells.
FAU - Wang, X
AU  - Wang X
AD  - Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, 
      Newark, NJ 07103, USA.
FAU - Wang, T-T
AU  - Wang TT
FAU - White, J H
AU  - White JH
FAU - Studzinski, G P
AU  - Studzinski GP
LA  - eng
GR  - R01 CA044722/CA/NCI NIH HHS/United States
GR  - R01 CA044722-16/CA/NCI NIH HHS/United States
GR  - R01-CA44722-16/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060529
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (ZK159222)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (KSR-1 protein kinase)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - 5' Flanking Region/*genetics
MH  - Calcitriol/analogs & derivatives/*metabolism/pharmacology
MH  - Cell Differentiation/drug effects
MH  - Gene Expression Regulation, Neoplastic
MH  - HL-60 Cells
MH  - Humans
MH  - Leukemia/*enzymology/*genetics/pathology
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Biosynthesis
MH  - Protein Kinases/*genetics
MH  - Receptors, Calcitriol/antagonists & inhibitors/metabolism
MH  - Signal Transduction
MH  - Up-Regulation
MH  - Vitamin D Response Element
PMC - PMC2843694
MID - NIHMS170005
EDAT- 2006/05/30 09:00
MHDA- 2006/12/14 09:00
PMCR- 2010/03/22
CRDT- 2006/05/30 09:00
PHST- 2006/05/30 09:00 [pubmed]
PHST- 2006/12/14 09:00 [medline]
PHST- 2006/05/30 09:00 [entrez]
PHST- 2010/03/22 00:00 [pmc-release]
AID - 1209697 [pii]
AID - 10.1038/sj.onc.1209697 [doi]
PST - ppublish
SO  - Oncogene. 2006 Nov 9;25(53):7078-85. doi: 10.1038/sj.onc.1209697. Epub 2006 May 
      29.