Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARα and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways

✍ Scribed by Philip J. Hughes; Yi Zhao; Roshantha A. Chandraratna; Geoffrey Brown

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 377 KB
• Volume: 97
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20579

✦ Synopsis

Abstract

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 α (RARα). Experiments with synthetic RAR and RXR agonists and antagonists suggest that RARα/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 PKCα and PKCδ 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. © 2005 Wiley‐Liss, Inc.