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(American Journal of Pathology. 2003;162:897-905.)
© 2003 American Society for Investigative Pathology

PTOV-1, a Novel Protein Overexpressed in Prostate Cancer, Shuttles between the Cytoplasm and the Nucleus and Promotes Entry into the S Phase of the Cell Division Cycle

Anna Santamaría^*, Pedro L. Fernández, Xavier Farré, Patricia Benedit^*, Jaume Reventós^*, Juan Morote^*, Rosanna Paciucci^* and Timothy M. Thomson^*

From the Unitat de Recerca Biomèdica,^* Hospital Vall d’Hebrón, Barcelona; the Departamento de Anatomía Patológica, Institut d’Investigacion Biomédiques August Pi i Sunyer (IDIBAPS), Hospital Clínico and Universidad de Barcelona, Barcelona; the Servicio de Urología, Hospital Vall d’Hebrón, Barcelona; and the Instituto de Biología Molecular, Consejo Superior de Investigaciones Científicas, Barcelona, Spain

PTOV1 was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer. The PTOV1 protein consists of two novel protein domains arranged in tandem, without significant similarities to known protein motifs. By immunohistochemical analysis, we have found that PTOV1 is overexpressed in 71% of 38 prostate carcinomas and in 80% of samples with prostate intraepithelial neoplasia. High levels of PTOV1 in tumors correlated significantly with proliferative index, as assessed by Ki67 immunoreactivity, and associated with a nuclear localization of the protein, suggesting a functional relationship between PTOV1 overexpression, proliferative status, and nuclear localization. In quiescent cultured prostate tumor cells, PTOV1 localized to the cytoplasm, being excluded from nuclei. After serum stimulation, PTOV1 partially translocated to the nucleus at the beginning of the S phase. At the end of mitosis, PTOV1 exited the nucleus. Transient transfection of chimeric green fluorescent protein-PTOV1 forced the entry of cells into the S phase of the cell cycle, as shown by double fluorescent imaging for green fluorescent protein and for Ki67, and also by flow cytometry. This was accompanied by greatly increased levels of cyclin D1 protein in the transfected cells. These observations suggest that overexpression of PTOV1 can contribute to the proliferative status of prostate tumor cells and thus to their biological behavior.

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