摘要：

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulates the activity of steroid sulphatase (STS) in myeloid cells [Hughes et al., [ 2001 ], [ 2005 ]]. This was attenuated by inhibitors of phospholipase D (PLD) ( n -butanol, 2,3-diphosphoglyceric acid, C2-ceramide) and phosphatidate phosphohydrolase (PAP) (propranolol and chlorpromazine), but was unaffected by inhibitors of phospholipase C. The 1,25(OH)2D3-induced STS activity was also attenuated by inhibitors of protein kinase C and protein kinase C (Go 6976, HBDDE and rottlerin), but not by an inhibitor of protein kinase C (LY379196). Additionally, 1,25(OH)2D3-induced STS activity was attenuated by inhibitors of RAS (manumycin A), RAF (GW5074), MEK (PD098059 and U1026) and JNK (SP600125), but not p38 (PD169316). 1,25(OH)2D3 produced a rapid and long lasting stimulation of the ERK-MAP kinase signalling cascade in HL60 myeloid leukaemic cells. This non-genomic effect of 1,25(OH)2D3 blocked by pharmacological antagonists of nuclear vitamin D receptors (VDRnuc) and does not appear to require hetero-dimerisation with the retinoid-X receptor (RXR). Inhibitors of the Src tyrosine kinase (PP1), RAS (manumycin A), RAS-RAF interactions (sulindac sulphide and RAS inhibitory peptide), RAF (GW5074 or chloroquine), and protein kinase C (HBDDE) abrogated the 1,25(OH)2D3-stimulated increase in ERK-MAP kinase activity. Taken together, these results show that 1,25(OH)2D3/VDRnuc activation of the RAS/RAF/ERK-MAP kinase signalling pathway plays an important role in augmenting STS activity in human myeloid leukaemic cell lines. J. Cell. Biochem. 98: 590-617, 2006. ? 2006 Wiley-Liss, Inc.

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