Abstract
In a search for molecular markers of progression in prostate cancer by means of differential display, we have identified a new gene, which we have designated PTOV1. Semiquantitative RT–PCR has established that nine out of 11 tumors overexpress PTOV1 at levels significantly higher than benign prostatic hyperplasia or normal prostate tissue. The human PTOV1 protein consists almost entirely of two repeated blocks of homology of 151 and 147 amino acids, joined by a short linker peptide, and is encoded by a 12-exon gene localized in chromosome 19q13.3. A Drosophila melanogaster PTOV1 homolog also contains two tandemly arranged PTOV blocks. A second gene, PTOV2, was identified in humans and Drosophila, coding for proteins with a single PTOV homology block and unrelated amino- and carboxyl-terminal extensions. A 1.8-Kb PTOV1 transcript was detected abundantly in normal human brain, heart, skeletal muscle, kidney and liver, and at low levels in normal prostate. Immunocytochemical analysis and expression of chimeric GFP-PTOV1 proteins in cultured cells showed a predominantly perinuclear localization of PTOV1. In normal prostate tissue and in prostate adenomas, PTOV1 was undetectable or expressed at low levels, whereas nine out of 11 prostate adenocarcinomas showed a strong immunoreactivity, with a focal distribution in areas of carcinoma and prostatic intraepithelial neoplasia. Therefore, PTOV1 is a previously unknown gene, overexpressed in early and late stages of prostate cancer. The PTOV homology block represents a new class of conserved sequence blocks present in human, rodent and fly proteins.
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Acknowledgements
We are grateful to G Parra and R Guigó for expert assistance in the prediction of gene structures, to F Munell for continued support, and to R Serrano for technical help. This work was funded by grants FIS 98/0199 (to J Reventós), PB97-1170 (to TM Thomson), SAF97-0084 and Marató TV3 (to R Paciucci). P Benedit is a recipient of a fellowship from the CIRIT, Catalunya, Spain. M Valeri was supported by a studentship from the Fundació per a la Recerca Vall d'Hebrón, Barcelona.
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Benedit, P., Paciucci, R., Thomson, T. et al. PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks. Oncogene 20, 1455–1464 (2001). https://doi.org/10.1038/sj.onc.1204233
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DOI: https://doi.org/10.1038/sj.onc.1204233
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