Clusterin over-expression modulates proapoptotic and antiproliferative effects of 1,25(OH)2D3 in prostate cancer cells in vitro.
J Steroid Biochem Mol Biol
; 103(3-5): 721-5, 2007 Mar.
Article
en En
| MEDLINE
| ID: mdl-17224269
ABSTRACT
Prostate cancer is the most commonly diagnosed cancer in the majority of western countries. Due to their antiproliferative and proapoptotic activity, vitamin D analogues have been introduced recently as an experimental therapy for prostate cancer. Clusterin (CLU) is a glycoprotein that has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, and a secretory form (sCLU) is pro-survival. In this study, we analyzed whether proapoptotic and antiproliferative effects of 1,25(OH)(2)D(3) on LNCaP prostate cancer cells are modulated by expression of sCLU. Using colony forming assay, we studied the effect of treatment with different doses of 1,25(OH)(2)D(3) (10(-6), 10(-7), 10(-10)M) on proliferation of LNCaP cells that were stable transfected and over-express sCLU (LNT-1) as compared to empty vector-transfected cells (LN/C). We also measured apoptosis using TUNEL assay. sCLU over-expression protected against both antiproliferative (30%) and proapoptotic (15%) effects of 1,25(OH)(2)D(3), although this effect was statistically not significant. In conclusion, our findings demonstrate that expression of sCLU modulates growth regulatory effects of 1,25(OH)(2)D(3) in prostate cancer indicating that CLU interferes with vitamin D signalling pathways.
Buscar en Google
Colección:
01-internacional
Asunto principal:
Neoplasias de la Próstata
/
Calcitriol
/
Regulación Neoplásica de la Expresión Génica
/
Apoptosis
/
Clusterina
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Alemania