Functional Interactions of the TACC2 Breast Tumor Suppressor Gene and Its Relevance to Breast Tumor Progression

摘要

Dysregulation of the human Transforming acidic coiled coil (TACC) genes is thought to be important in the development of breast cancer. However, the mechanism by which they function still remains to be clarified. We have demonstrated that the full length TACC2 protein can inhibit the tumorigenic phenotype of certain breast cancer cells. We have now performed mapping experiments that demonstrate that the conserved coiled coil domain is critical for this effect. We have confirmed that the histone acetyltransferases (HATs), hCGN5, and pCAF bind to this domain, suggesting that interaction between TACC2 and these proteins may be critical for the maintenance of the normal mammary epithelium. Although breast cancer cells do not significantly express hGCN5, they do express pCAF. A biological function of TACC2 was indicated by its effect to efficiently negate the in vitro suppression of DNA-dependent protein kinase (DNA-PK) mediated pCAF activity. Taken together these findings appear to imply that one of the functions of TACC2 is to counteract a negative modulator of his tone acetylase activity, thereby potentially regulating the expression of genes involved in the maintenance of normal mammary development.