25-hydroxy-vitamin d metabolism in human colon cancer cells during tumor progression.
作者： Petra Bareis , Giovanna Bises , Martin G. Bischof , Heide S. Cross , Meinrad Peterlik
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摘要: RT-PCR analysis showed elevated expression of 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase) and D-24-hydroxylase (24-OHase) in well differentiated human colon carcinomas comparison to normal mucosa. Further tumor progression is associated with a rise 1alpha-OHase but no significant change 24-OHase mRNA expression. Accordingly, HPLC 25-hydroxy-vitamin D3 metabolism freshly isolated cells indicated that moderately cancers situ are able produce 1alpha,25-dihydroxyvitamin (1alpha,25-(OH)2D3) convert it through activity into side-chain modified metabolites, 1,24,25-(OH)3-D3 1,25-(OH)2- 24-oxo-D3. Likewise, 25-(OH)-D3 metabolized 24,25-(OH)2D3, 23,25-(OH)2D3, 23,25-(OH)2-24-oxo-D3. Poorly-differentiated expressed low levels mRNA, whereas was even over-expressed. vitamin D primary culture cell clones strongly suggested the extent endogenously produced 1alpha,25-(OH)2-D3 inversely related activity, which could thus limit antimitotic efficacy particularly at late stages cancer progression.
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