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

Orv Hetil. 2016 Nov;157(48):1910-1918. doi: 10.1556/650.2016.30592.
[Article in Hungarian]

Abstract

Introduction: 1,25-Dihydroxy vitamin D3 mediates antitumor effects in hepatocellular carcinoma.

Aim: We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D3-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 D3, providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.

Keywords: CYP24A1; CYP27B1; D-vitamin; hepatocellular carcinoma; hepatocellularis carcinoma; vitamin D.

MeSH terms

  • 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

Substances

  • RNA, Messenger
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase