We have reported that dibutyryl cAMP (dbcAMP), an activator of cAMP-dependent protein kinase (PKA), potentiated the effects of 1α, 25-dihydroxyvitamin D
3(1, 25-(OH)
2D
3)-induced 24-hydroxylation activity inHL-60 cells by increasing 1, 25-(OH)
2D
3 receptor (VDR). The present study demonstrated that 12-
O-tetradecanoylphorbol- 13-acetate (TPA), a potent phorbol ester, also potentiated the effect of 1, 25-(OH)
2D
3 on HL-60 cells and that TPA and dbcAMP acted in a synergistic manner to enhance the effect of 1, 25-(OH)
2D
3. It is interesting that TPA induced 24-hydroxylation activity far more efficiently than dbcAMP, in addition to their effects in increasing VDR. TPA increased basal levels of
c-fos mRNA to the maximum by 1h after the treatment, whereas dbcAMP failed to affect
c-fos gene expression. Together with the previous data indicating the presence of AP-1-like sequence in the promoter of 24-hydroxylase gene, it was suggested that TPA potentiated the effect of 1, 25-(OH)
2D
3 through an activation of
c-fos gene expression. This notion was further supported by the data showing that TPA and dbcAMP also acted in a synergistic manner to activate
c-fos gene expression. Neither TPA nor dbcAMP affected
c-jun early response gene in the HL-60 clone used in the present study. The present study suggested that the activation of early
c-fos response gene by TPA might be another mechanism to enhance the effect of 1, 25-(OH)
2D
3, besides up-regulation of VDR.
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