Inhibition of proteasome activity by bortezomib in renal cancer cells is p53 dependent and VHL independent.

ABSTRACT:

Background

Antiproliferative effects of proteasome inhibitors are suggested to be primarily due to effects on nuclear factor-kappaB (NF-kappaB)-dependent pathways and the induction of apoptosis. The objective of this study was to elucidate the mechanistic basis for the antiproliferative effects of the proteasome inhibitor, bortezomib, in human clear cell renal cell cancer cells (CCRCC).

Materials and methods

von Hippel Lindau (VHL) mutation/methylation status and cytotoxic response to bortezomib was determined in a panel of CCRCC cell lines. Effects on target protein/gene expression and the role of p53 in bortezomib-mediated cytotoxicity, inhibition of proteasome activity, survivin transcript and protein expression as well as induction of p21 expression was determined in CCR

SUBMITTER: Vaziri SA 

PROVIDER: S-EPMC4141551 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature