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

• Published in: Orvosi hetilap Vol. 157; no. 48; p. 1910
• Main Authors: Horváth, Evelin, Balla, Bernadett, Kósa, János, Lakatos, Péter András, Lazáry, Áron, Németh, Dániel, Jozilan, Hasan, Somorácz, Áron, Korompay, Anna, Gyöngyösi, Benedek, Borka, Katalin, Kiss, András, Kupcsulik, Péter, Schaff, Zsuzsa, Szalay, Ferenc
• Format: Journal Article
• Language: Hungarian
• Published: Hungary 01.11.2016
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism; Carcinoma, Hepatocellular - metabolism; Cholestanetriol 26-Monooxygenase - metabolism; Cytochrome P450 Family 2 - metabolism; Gene Expression - drug effects; Humans; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; RNA, Messenger - metabolism; Vitamin D3 24-Hydroxylase - metabolism; CYP27B1; CYP24A1; hepatocellularis carcinoma; vitamin D; hepatocellular carcinoma; D-vitamin
• ISSN: 0030-6002
• DOI: 10.1556/650.2016.30592

1,25-Dihydroxy vitamin D mediates antitumor effects in hepatocellular carcinoma. We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D -inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. 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. 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. 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 , providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.