Analysis of the TACC1 Gene From the 8p11 Chromosome Region Frequently Amplified in Metastasizing Breast Cancer
Final rept. 1 Jun 1999-1 Mar 2004
HEALTH RESEARCH INC BUFFALO NY
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The TACC1 gene was isolated from a region of chromosome 8pll which shows amplification in breast cancers, especially those which show metastasis to the lymph nodes. Preliminary studies showed that overexpression of TACC1 in mouse fibroblasts cause morphological transformation. We have now shown, using immunohistochemistry and immunoprecipitation, that TACC1 is present I the cytoplasm and the nucleus and furthermore that it can associate with the centrosome and mitotic spindle apparatus during mitosis. Using the full length TACC1 protein as bait to screen a human mammary epithelial cDNA library, we have identified several proteins that interact with TACC1. TACC1 interacts with the cytosketal and microtubule associated proteins ch-TOG and FHL3. TACC1 also associates with proteins involved in chromatin remodeling CAS4l, transcription FHL2 and 3, and RNA splicing and degradation L-Sm7 . This suggests that TACC1 can form multiple complexes, dysregulation of which may be an important step during progression of breast tumors. Further characterization of the intracellular pathways that use TACC1 for their function will help further understand its role in breast tumorigenesis.
- Anatomy and Physiology
- Medicine and Medical Research