WWOX as a Critical Signal Mediator in Breast Cancer

Studying WWOX as a critical signal mediator in breast cancer and determination of the mechanisms by which WWOX affects the breast cancers response to Tamoxifen, in addition to ErbB2, AP2γ, AP2α and PKA-RIα effects The WWOX gene at FRA16D is frequently silenced in cancers, and has recently been shown to suppress growth of lung and breast cancer. In addition to deletions and translocations the fragile WWOX gene, is frequently silenced by hypermethylation of its CpG dinucleotide-rich promoter regions. Because promoter hypermethylation is responsible for silencing WWOX in a large fraction of breast and lung cancers,pharmacologic therapy to restore expression of WWOX and other tumor suppressors, for prevention or treatment offers a potentially efficacious approach. WWOX encodes a 46 kDa protein that contains two WW domains that mediate protein-protein interactions and a short-chain oxidoreductase (SDR) domain.