Functional Interactions of the TACC2 Breast Tumor Suppressor Gene and Its Relevance to Breast Tumor Progression
Abstract
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 lull length TACC2 protein can inhibit the tumorigenic phenotype of certain breast cancer cells. Similarly, the TACC2 interacting protein, hGCN5 can also reduces breast cancer cell survival. The catalytic domain of this histone acetyltransferase is critically important for this effect. Thus, modulation of hGCN5 and/or pCAF activity may represent a mechanism by which TACC2 may exert its tumor suppressive properties. We have furthered our analysis of TACC2 mediated transcriptional events by examining the effects of TACC2 on the BRCAl mediated regulation of the p21 gene. Our initial data suggests that basal levels of p21 and STAT1 are decreased in TACC2 transfected cell lines. Independently, we have found an interaction between the TACCs and the FHL family of transcriptional regulators. These latter proteins coactivate or corepress transcription, in a promoter specific context. We are now examining whether TACC2 possesses similar properties, or alternatively acts as a transcriptional switch, as previously indicated for the CBF- l/RBP-Jk splice variant of FHLl in the Notch signaling pathway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA428238
Entities
People
- Ivan H. Still
Organizations
- Health Research, Incorporated