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Abstract

Very little is known about the etiology of ovarian cancer. However, studies have shown that occupational exposure to polycyclic aromatic hydrocarbons (PAHs) and tobacco smoking can increase ovarian cancer risk. Previously, we have determined that 100% of ovarian tumors show loss or aberrant subcellular localization of TACC3 (transforming acidic coiled coil 3) relative to the normal ovarian surface epithelium (OSE). In mice, a role for TACC3 in the cellular response to PAH has been defined. However, comparable studies for human TACC3 has not been performed. In this report, we show that specific knockdown of TACC3 in human ovarian cancer cells increases the basal level, and distorts the PAH-induced expression, of genes involved in metabolizing the procarcinogen PAH benzo[a]pyrene to its DNA damaging epoxide. In addition, we demonstrate that PAH stabilizes the TACC3 protein and induces the export of TACC3 and one of its binding partners, Ku70, from the nucleus. This parallels the subcellular distribution of TACC3 in those ovarian cancers that express TACC3. These data suggest that functional downregulation of TACC3 could aid tumor progression by altering cellular responses to chemical carcinogens and the DNA damage that they induce.

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