Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon

Amplification of several chromosomal regions have been observed in human br east carcinomas. One such region, 8p11, is amplified in 10-15% of tumor sam ples, Although the FGFR1 gene is located close to this region, and is often included within the amplicon, the observation that tumors exhibiting 8p11 amplification do not always overexpress FGFR1 suggests that another gene lo cated close to FGFR1 is involved in the tumorigenic process. We now report the precise location of four expressed sequence tags (ESTs) within this reg ion and the cloning of a novel gene, designated TACC1 (transforming acidic coiled coil gene 1), which encodes an 8 kb transcript and which is expresse d at high levels during early embryogenesis. Constitutive expression of thi s gene under the control of the cytomegalovirus (CMV) promoter in mouse fib roblasts, results in cellular transformation and anchorage independent grow th, suggesting that inappropriate expression can impart a proliferative adv antage. This observation raises the possibility that amplification of TACC1 could promotemalignant growth, thereby making TACC1 an attractive candidat e for the gene promoting tumorigenicity as a result of the 8p11 amplificati on in human breast cancers.