3.9 Article

Vitamin D metabolism and signaling in human hepatocellular carcinoma and surrounding non-tumorous liver

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ORVOSI HETILAP
卷 157, 期 48, 页码 1910-1918

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AKADEMIAI KIADO ZRT
DOI: 10.1556/650.2016.30592

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hepatocellular carcinoma; CYP24A1; CYP27B1; vitamin D

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Introduction: 1,25-Dihydroxy vitamin D-3 mediates antitumor effects in hepatocellular carcinoma. Aim: We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D-3-inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. Methods: Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. Results: Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver ( p<0.05). The majority of the HCC samples expressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. Conclusions: The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D-3, providing an escape mechanism from the anti-tumor effect.

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