Document Detail

Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways.
MedLine Citation:
PMID:  16178010     Owner:  NLM     Status:  MEDLINE    
All-trans retinoic acid and 9-cis-retinoic acid stimulate the activity of steroid sulfatase in HL60 acute myeloid leukemia cells in a concentration- and time-dependent manner. Neither of these 'natural retinoids' augmented steroid sulfatase activity in a HL60 sub-line that expresses a dominant-negative retinoic acid receptor alpha (RARalpha). Experiments with synthetic RAR and RXR agonists and antagonists suggest that RARalpha/RXR heterodimers play a role in the retinoid-stimulated increase in steroid sulfatase activity. The retinoid-driven increase in steroid sulfatase activity was attenuated by inhibition of phospholipase D (PLD), but not by inhibitors of phospholipase C. Experiments with inhibitors of protein kinase C (PKC) show that PKCalpha and PKCdelta play an important role in modulating the retinoid-stimulation of steroid sulfatase activity in HL60 cells. Furthermore, we show that pharmacological inhibition of the RAF-1 and ERK MAP kinases blocked the retinoid-stimulated increase in steroid sulfatase activity in HL60 cells and, by contrast, inhibition of the p38-MAP kinase or JNK-MAP kinase had no effect. Pharmacological inhibitors of the phosphatidylinositol 3-kinase, Akt, and PDK-1 also abrogated the retinoid-stimulated increase in steroid sulfatase activity in HL60 cells. These results show that crosstalk between the retinoid-stimulated genomic and non-genomic pathways is necessary to increase steroid sulfatase activity in HL60 cells.
Philip J Hughes; Yi Zhao; Roshantha A Chandraratna; Geoffrey Brown
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  97     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-17     Completed Date:  2006-06-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  327-50     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Wiley-Liss, Inc.
Division of Immunity and Infection, The Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism*,  physiology
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases / metabolism*
HL-60 Cells
Leukemia, Myeloid / enzymology*
MAP Kinase Signaling System
Phospholipase D / metabolism
Protein Kinases / metabolism
Receptors, Retinoic Acid / metabolism*,  physiology
Retinoid X Receptors / metabolism
Steryl-Sulfatase / metabolism*
Tretinoin / agonists,  antagonists & inhibitors,  metabolism*,  physiology*
Reg. No./Substance:
0/Receptors, Retinoic Acid; 0/Retinoid X Receptors; 0/retinoic acid receptor alpha; 302-79-4/Tretinoin; EC 2.7.-/Protein Kinases; EC 3-Kinase; EC Signal-Regulated MAP Kinases; EC D; EC

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