The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding.

ABSTRACT:

Background

The WW domain containing protein WWOX has been postulated to behave as a tumor suppressor in breast and other cancers. Expression of this protein is lost in over 70% of ER negative tumors. This prompted us to investigate the phenotypic and gene expression effects of loss of WWOX expression in breast cells.

Methods

Gene expression microarrays and standard in vitro assays were performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic analyses were used to identify gene networks and transcriptional regulators affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays, ChIP, confocal microscopy and in silico analyses were employed to determine the effect

SUBMITTER: Ferguson BW 

PROVIDER: S-EPMC3871008 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature