A D-vitamin metabolizmusa humán hepatocellularis carcinomában és az azt körülvevő tumormentes májszövetben | Vitamin D metabolism and signaling in human hepatocellular carcinoma and surrounding non-tumorous liver

Absztrakt Bevezetes: Az 1,25-dihidroxi-D 3 -vitamin tumorellenes hatasa hepatocellularis carcinomaban mar reszben ismert. Celkitűzes: Az 1,25-dihidroxi-D 3 -vitamint inaktivalo CYP24A1-mRNS- es feherjeexpresszio, az aktivalo CYP27B1- es a VDR-mRNS-expresszio mertekenek osszehasonlitasa human hepatocellularis carcinomaban es az azt korulvevő tumormentes majszovetben. Modszer: 13 beteg friss fagyasztott majszovetmintajat a CYP24A1-mRNS- es feherje-, 36 beteg paraffinba agyazott majszovetmintajat hasznaltuk a VDR- es a CYP27B1-mRNS-expresszio kimutatasara. Az mRNS-expressziot RT-PCR-rel, a feherjet immunhisztokemiai vizsgalatokkal mertuk. Eredmenyek: A hepatocellularis carcinomamintak tobbsegeben kimutathato volt a CYP24A1-mRNS-expresszio, mig a nem tumoros majszovetmintak egyikeben sem. A CYP27B1- es VDR-expresszio szignifikansan alacsonyabb hepatocellularis carcinomaban a tumormentes majszovethez kepest (p<0,05). A CYP24A1-mRNS-expressziot feherjeszintezis koveti. Kovetkeztetesek: A CYP24A1 inaktivalo enzim jelenlete, az aktivalo CYP27B1 es a VDR csokkent expresszioja human hepatocellularis carcinomaban a D-vitamin csokkent helyi aktivitasara enged kovetkeztetni, mint egy menekulő mechanizmus a tumor reszeről a D-vitamin antitumorhatasa ellen. Orv. Hetil., 2016, 157(48), 1910–1918. | Abstract 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. Orv. Hetil., 2016, 157(48), 1910–1918.