ANTI-PROLIFERATIVE EFFECTSOF1 ,25-DIHYDROXYVITAMIND3ONKAPOSISARCOMACELL-

PARDO VG; FACCHINETTI MARIA M; RUSSO DE BOLAND A

Mar del Plata

Congreso; 43 Reunion Anual de la Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2007

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

The aim of this work was to study the effects of the steroid hormone 1 ,25-dihydroxy-vitamin D3 (1,25D) on the proliferation and apoptosis of endothelial cells transformed by the viral G proteincoupled receptor (vGPCR), the constitutively active chemokine receptor encoded by human herpesvirus 8 (HHV8), also known as Kaposi sarcoma herpesvirus. For this purpose, SKSV-40 immortalized murine endothelial cells (SVECs; kindly provided by Dr. Silvio Gutkind, NIH- USA) stably expressing vGPCR fulllength were used. MTS proliferation assays and FACS cell cycle analysis showed that 1,25D decreased SVEC-vGPCR proliferation, in a time and dose-dependent manner, induced G1 phase arrest and increased subG0/G1 population. VDR protein levels were induced upon treatment with 10 nM 1,25D, whereas cyclin D1 protein levels decreased and p53 levels remain unchanged. Induced VDR protein levels were blocked by cycloheximide. Confocal microscopy studies indicated that under basal conditions native VDR has cytoplasmic and nuclear localization. VDR translocation to the nucleus was observed within 15 min and also at 48 h of 1,25D exposure. Taken together, these results indicate that 1,25D exerts antiproliferative effects in the Kaposi sarcoma cell-like model regulating cyclinD1andVDRprotein expression.