期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 285, 期 4, 页码 1012-1017出版社
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2001.5289
关键词
1 alpha,25-dihydroxyvitamin D-3; large intestine; adenocarcinoma; primary culture; vitamin D metabolism; side-chain oxidation; vitamin D-1 alpha-hydroxylase; CYP 1 alpha; vitamin D-24-hydroxylase; CYP 24
RT-PCR analysis showed elevated expression of 25-hydroxyvitamin D1 alphaa-hydroxylase (1 alpha -OHase) and of 25-hydroxyvitamin D-24-hydroxylase (24-OHase) in well differentiated human colon carcinomas in comparison to normal mucosa. Further tumor progression is associated with a rise in 1 alpha -OHase but with no significant change in 24-OHase mRNA expression. Accordingly, HPLC analysis of 25-hydroxy-vitamin D-3 metabolism mi freshly isolated tumor cells indicated that well to moderately differentiated colon cancers in situ are able to produce 1 alpha ,25-dihydroxyvitamin D-3 (1 alpha ,25-(OH)(2)D-3) and convert it through 24-OHase activity into side-chain modified metabolites, 1,24,25-(OH)(3)-D-3 and 1,25-(OH)(2)-24-oxo-D-3. Likewise, 25-(OH)-D-3 is metabolized into 24,25-(OH)(2)D-3, 23,25-(OH)(2)D-3, and 23,25-(OH)(2)-24-oxo-D-3. Poorly-differentiated cancers expressed low levels of 1 alpha -OHase mRNA, whereas 24-OHase was even overexpressed. RT-PCR and HPLC analysis of vitamin D metabolism in primary culture cell clones strongly suggested that the extent of endogenously produced 1 alpha ,25(OH)(2)-D-3 was inversely related to 24-OHase activity, which could thus limit the antimitotic efficacy of la,25(OH)2-D3 particularly at late stages of colon cancer progression. (C) 2001 Academic Press.
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