Abstract
In this article we show that 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) 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 (VDRnuc) 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)2D3 (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)2D3- 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)2D 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)2D3- stimulated increase in steroid sulphatase activity in myeloid leukaemic cells.
Original language | English (US) |
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Pages (from-to) | 1551-1572 |
Number of pages | 22 |
Journal | Journal of Cellular Biochemistry |
Volume | 103 |
Issue number | 5 |
DOIs | |
State | Published - Apr 1 2008 |
Externally published | Yes |
Keywords
- Genomic and non-genomic signalling
- Myeloid cells
- Phosphatidylinositol 3-kinase
- Steroid sulphatase
- Vitamin D receptor
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology