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Tat-interacting protein 30 (TIP30), a transcriptional repressor for ERα-mediated transcription, possesses several characteristics of a tumor suppressor in certain human and mouse cells. It is reported that deletion of TIP30 gene preferentially increases tumorigenesis in the female knockout mice. Here, we analyzed TIP30 gene expression in the databases of several DNA microarray studies of human prostate cancer and show that TIP30 is specifically overexpressed in metastatic prostate cancers. We demonstrate that TIP30 nuclear expression is associated with prostate cancer progression and metastasis by immunohistochemical analysis in primary and metastatic prostate cancers. Consistent with these data, we also show that knockdown of TIP30 expression, through use of a short hairpin RNA-expressing plasmid, suppresses the cellular growth of PC3 and LNCaP prostate cancer cells. Ectopic overexpression of TIP30 stimulates metastatic potential of prostate cancer cells in anin vitroinvasion assay, whereas knockdown of TIP30 inhibits the prostate cancer cells invasion. Finally, we demonstrate that ectopic overexpression of TIP30 enhances androgen receptor mediated transcription, whereas knockdown of TIP30 results in a decreased transcription activity. These data provide evidence that TIP30 plays a role in prostate cancer progression and that TIP30 overexpression may promote prostate cancer cell growth and metastasis. © 2008 Wiley-Liss, Inc.