The vitamin D receptor-mediated activation of phosphatidylinositol 3-kinase (PI3Kα) plays a role in the 1α,25-dihydroxyvitamin D3-stimulated increase in steroid sulphatase activity in myeloid leukaemic cell lines

✍ Scribed by Philip J. Hughes; Jimmy S. Lee; Neil E. Reiner; Geoffrey Brown

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 338 KB
• Volume: 103
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21545

✦ Synopsis

Abstract

In this article we show that 1α,25‐dihydroxyvitamin D~3~ (1α,25(OH)~2~D~3~) stimulates the activity of the class IA phosphatidylinositol 3‐kinase PI3Kα and its downstream target Akt in HL60, U937 and THP‐1 myeloid leukaemic cell lines. Furthermore, we show that the classical nuclear vitamin D receptor (VDR~nuc~) is involved in this activation of the PI3K/Akt signalling in these cell lines. We have previously shown that the activity of steroid sulphatase is stimulated in HL60, U937 and THP‐1 myeloid leukaemic cell lines by 1α,25(OH)~2~D~3~ (Hughes et al., [2001] Biochem J 355:361–371; Hughes et al., [2005] J Cell Biochem 94:1175–1189; Hughes and Brown [2006] J Cell Biochem 98:590–617). In this article we show that the 1α,25(OH)~2~D~3~‐stimulated increase in signalling via the PI3K/Akt pathway plays a role in the increase in steroid sulphatase activity in the HL60 U937 and THP‐1 cell lines. We used a variety of pharmacological and biochemical approaches to show that activation of PI3Kα mediates the 1α,25(OH)~2~D~3~‐stimulated increase in steroid sulphatase activity in myeloid leukaemic cells. We also show that the PI3K/Akt dependent activation of NF‐κB plays a role in the 1α,25(OH)~2~D~3~‐stimulated increase in steroid sulphatase activity in myeloid leukaemic cells. J. Cell. Biochem. 103: 1551–1572, 2008. © 2007 Wiley‐Liss, Inc.