Abstract
WWOX (WW domain-containing oxidoreductase) gene, located on chromosome 16q 23.3-24.1 in the region recognized as the common fragile site FRA16D is considered to be a tumor suppressor gene involved in various cancers: breast, ovarian, prostate, esophageal, lung, pancreatic, gastric and hepatic. The aim of this study was to describe (i) putative protein interactions of WWOX (ii) the molecular mechanisms of tumor suppressor activity (iii) present an overview of WWOX in relation to nervous system and breast, prostate and ovarian cancers. WWOX expression is up-regulated in endocrine organs indicating its importance in these tissues. In many cancers WWOX expression is down-regulated and low WWOX expression is related to poor prognosis. All the evidence suggest that WWOX can be considered as a new tumor suppressor gene and target for gene therapy due to the association of high WWOX expression with improved disease free survival.
Highlights
Chromosomal and genomic abnormalities affecting chromosome 16q have been frequently reported in cytogenetic and allelotypic studies of various epithelial tumors
Reduced WWOX staining (> 10 %) in normal breast tissue was found in post-menopausal women or in breast cancer patients exposed to neoadjuvant chemotherapy, suggesting that WWOX expression may be associated with level of steroid hormone expression and can be affected by chemotherapy
Further studies will be necessary to prove whether loss of WWOX expression is an early causative event of breast cancer, for at least in a subset of tumors or, whether this event predominantly occurs during the progression of breast carcinomas
Summary
Chromosomal and genomic abnormalities affecting chromosome 16q have been frequently reported in cytogenetic and allelotypic studies of various epithelial tumors. WWOX expression is up-regulated in endocrine organs such as testis, ovary and breast, indicating the importance of WWOX in these tissues[8]. It is likely that loss of WWOX in tumor cells may result in reduced p73 apoptotic activity in cytoplasm[38].
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