کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9892216 | 1541105 | 2005 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Epigenetic regulation of Vitamin D hydroxylase expression and activity in normal and malignant human prostate cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
It was previously suggested that the 25-Vitamin-D3-1α-hydroxylase (CYP27B1) is downregulated during human prostate tumor pathogenesis while the catabolic 25-Vitamin-D3-24-hydroxylase (CYP24) expression is increased. The latter could lead to resistance against the antimitotic, prodifferentiating activity of 1,25-dihydroxycholecalciferol. Our hypothesis was that regulation of Vitamin D hydroxylase expression during prostate tumor progression might be under epigenetic control. We demonstrate by real time RT-PCR that PNT-2 human normal prostate cells indeed possess CYP27B1, but are practically devoid of CYP24 mRNA, whereas DU-145 cancer cells have constitutive expression of CYP24, and very low levels of CYP27B1 mRNA. Treatment of PNT-2 cells with the methylation inhibitor 5-aza-2â²-deoxycytidine together with the deacetylation inhibitor trichostatin A resulted in elevation of both CYP27B1 and CYP24 mRNA expression demonstrating that even in normal human prostate cells expression of Vitamin D hydroxylases may be under epigenetic control. In the DU-145 malignant cell line trichostatin A together with 5-aza-2â²-deoxycytidine increased CYP27B1 mRNA expression to a smaller extent than in normal cells, however this resulted in a highly significant increase in 1α-hydroxylation capacity. This demonstrates for the first time that synthesis of 1,25-dihydroxycholecalciferol in human prostate tumors could be reinitiated by epigenetic regulators.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 93, Issues 2â5, February 2005, Pages 167-172
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 93, Issues 2â5, February 2005, Pages 167-172
نویسندگان
Maya Khorchide, Daniel Lechner, Heide S. Cross,