Evidenze molecolari del ruolo antiproliferativo e pro-apoptotico della clusterina in cellule epiteliali prostatiche umane

The Clusterin (CLU) gene produces different forms of protein products which vary in their biological properties and distribution within the cell. Both the extra- and intracellular CLU forms regulate cell proliferation and apoptosis. Dis-regulation of CLU expression occurs in many cancer types, including prostate cancer. The role that CLU plays in tumorigenesis is still unclear. We found that CLU over-expression inhibited cell proliferation and induced apoptosis in prostate cancer cells. Here we show that depletion of CLU affects the growth of PC-3 prostate cancer cells. Following siRNA, all protein products quickly disappeared, inducing cell cycle progression and higher expression of specific proliferation markers (i.e. H3 mRNA, PCNA and cyclins A, B1 and D) as detected by RT-qPCR and Western blot. Quite surprisingly, we also found that the turnover of CLU protein is very rapid and tightly regulated by ubiquitin–proteasome mediated degradation. Inhibition of protein synthesis by cycloheximide showed that CLU half-life is less than 2 hours. All CLU protein products were found poly-ubiquitinated by co-immuniprecipitation. Proteasome inhibition by MG132 caused stabilization and accumulation of all CLU protein products, strongly inducing the nuclear form of CLU (nCLU) and committing cells to caspase-dependent death. In conclusion, proteasome inhibition may induce prostate cancer cell death through accumulation of nCLU, a potential tumour suppressor factor.

Grantor dc:publisher

Alma Mater Studiorum - Università di Bologna

Year dc:date

2008

Author dc:creator

• Rizzi, Federica Maria Angela <1972>

Contributors dc:contributor

• Casti, Amos

• BIO/10 Biochimica

Statement dc:rights

• info:eu-repo/semantics/restrictedAccess

Language dc:language

it

Identifier

urn:nbn:it:unibo-616
Rizzi, Federica Maria Angela (2008) Evidenze molecolari del ruolo antiproliferativo e pro-apoptotico della clusterina in cellule epiteliali prostatiche umane, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biochimica <https://amsdottorato.unibo.it/view/dottorati/DOT206/>, 20 Ciclo.

OAI identifier oai:identifier

oai:amsdottorato.cib.unibo.it:645