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

Santamaría, Anna; Fernández, Pedro; Farré, Xavier; Benedit, Patricia; Reventós, Jaume; Moróte, Juan; Paciucci, Rosanna; Thomson, Timothy M.

doi:10.1016/s0002-9440(10)63885-0

Cited by 48 publications

(87 citation statements)

References 30 publications

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“…The overexpression of PTOV1 in HG-PIN that are associated with cancer provides additional evidence to link HG-PIN as a precursor lesion to prostatic adenocarcinoma. Previous results showing the correlation between the high expression of PTOV1 in tumors with higher proliferative status and the capacity of PTOV1 to induce cell entry into the S phase of the cell cycle support this notion (2,3). In addition, the results shown here might also suggest that a subset of HG-PIN lesions, identified by PTOV1 expression, are ''predetermined'' to develop into malignant lesions.…”

Section: Discussionsupporting

confidence: 78%

“…Rabbit antisera against the peptide KRRPYSD-STAKLKR of PTOV1, and its purification by affinity chromatography, have been previously described (1,3).…”

Section: Methodsmentioning

confidence: 99%

“…In cultured prostate tumor cells, PTOV1 localized in the cytoplasm of quiescent cells and after serum stimulation, the protein partially translocated to the nucleus. Exogenous overexpression of tagged-PTOV1 induced the entry of cells into the S phase of the cell cycle, which was accompanied by increased levels of cyclin D1 in the transfected cells, suggesting that overexpression of PTOV1 could contribute to the proliferative status of prostate tumor cells and thus to their biological behavior (3).…”

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confidence: 99%

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PTOV1 Expression Predicts Prostate Cancer in Men with Isolated High-Grade Prostatic Intraepithelial Neoplasia in Needle Biopsy

Moróte¹,

Fernández²,

Alaña

et al. 2008

Clinical Cancer Research

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Purpose: To analyze the expression of PTOV1 in high-grade prostatic intraepithelial neoplasia (HG-PIN) and to explore its usefulness to predict prostate cancer in patients with isolated HG-PIN in needle biopsy (prostate needle biopsy). Experimental Design: PTOV1expression in HG-PIN lesions from 140 patients was analyzed by immunohistochemistry in a semiquantitative manner (Histo-score). HG-PIN derived from 79 radical prostatectomies for prostate cancer and from 11 cistoprostatectomies for bladder cancer without prostate cancer were used as positive and negative controls, respectively. Fifty patients with HG-PIN without concomitant cancer at their first prostate needle biopsy were chosen as the study group. Patients were followed by a mean of 2.5 repeated prostate needle biopsies (1-5), during a mean period of 12.4 months (1-39). Results: PTOV1expression in HG-PIN from radical prostatectomies showed a significantly higher Histo-score (162.6) compared with specimens from cistoprostatectomies (67.0). In the study group, PTOV1 expression was significantly higher in samples with cancer in the follow-up (11 patients, 22%) compared with samples in which cancer was not detected (151.4 versus 94.6). PTOV1expression was the only independent predictor of cancer in the multivariate analysis and the area under the curve was 0.803 (95% confidence interval, 0.728-0.878). A threshold of 100 for PTOV1 expression provided 90.9% sensitivity, 51.3% specificity, 34.5% positive predictive value, and 95.2% negative predictive value. Conclusions: PTOV1 is overexpressed in HG-PIN associated with cancer and is a potential marker for studying the carcinogenesis and progression of prostate cancer. Prostate needle biopsy with PTOV1 expression in HG-PIN above a threshold of 100 should be repeated immediately for the likely presence of undiagnosed cancer.Prostate tumor overexpressed-1 (PTOV1) was identified in our laboratory as a novel gene and protein during a screening for genes differentially expressed in prostate cancer. PTOV1 protein consists of two repeated blocks 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 (1). The expression of PTOV1 is regulated by androgens (2). By immunohistochemical analysis, PTOV1 was undetectable in normal prostate tissue and benign prostate hyperplasia, whereas a strong immunoreactivity was shown in areas of carcinoma and high-grade prostatic intraepithelial neoplasia (HG-PIN). The high expression of PTOV1 in tumors correlated with their proliferative status, assessed by Ki67 immunoreactivity, and associated with nuclear localization of the protein, suggesting a functional relationship between PTOV1 overexpression, proliferative status, and nuclear localization. In cultured prostate tumor cells, PTOV1 localized in the cytoplasm of quiescent cells and after serum stimulation, the protein partially translocated to the nucleus. Exogenous overexpression of tagged-PTOV1 induced the entry of cells into the S phase of the cell ...

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Section: Discussionsupporting

confidence: 78%

“…Rabbit antisera against the peptide KRRPYSD-STAKLKR of PTOV1, and its purification by affinity chromatography, have been previously described (1,3).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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PTOV1 Expression Predicts Prostate Cancer in Men with Isolated High-Grade Prostatic Intraepithelial Neoplasia in Needle Biopsy

Moróte¹,

Fernández²,

Alaña

et al. 2008

Clinical Cancer Research

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“…Potentially this effect may be related to an association between 14-3-3 and MKLP1. PTOV-1 is a mitogenic factor that migrates to the nucleus during S phase entry (48). It is therefore conceivable that association with 14-3-3 slows G 1 /S progression by cytoplasmic sequestration of PTOV-1.…”

Section: Discussionmentioning

confidence: 99%

Targeted Proteomic Analysis of 14-3-3ς, a p53 Effector Commonly Silenced in Cancer

Benzinger

Muster

Koch

et al. 2005

Molecular & Cellular Proteomics

171

138

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“…The protein PTOVI is overexpressed in 71% and 80% of pea and HGPIN cases, respectively, while it is expressed at low levels in normal prostate epithelium (3,5). PTOVI is expressed at high levels in neuroendocrine cells and in endothelial cells (9).…”

Section: Discussionmentioning

confidence: 99%

Is There a Role for Prostate Tumour Overexpressed-1 in the Diagnosis of HGPIN and of Prostatic Adenocarcinoma? A Comparison with α-Methylacyl CoA Racemase

Scarpelli

Mazzucchelli

Barbisan

et al. 2012

Int J Immunopathol Pharmacol

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Prostate Tumour Overexpressed-1 (PTOV1) was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer (PCa). α-Methyl-CoA racemose (AMACR) mRNA was identified as being overexpressed in PCa. PTOV1 and racemase were immunohistochemically evaluated in PCa, high-grade prostatic intraepithelial neoplasia (HGPIN), atrophy and normal-looking epithelium (NEp) in 20 radical prostatectomies (RPs) with pT2a Gleason score 6 prostate cancer with the aim of analyzing the differences in marker expression between PTOV1 and AMACR. The level of expression of PTOV1 and AMACR increased from NEp and atrophy through HGPIN, away from and adjacent to prostate cancer, to PCa. With the ROC curve analysis the overall accuracy in distinguishing PCa vs HGPIN away from and adjacent to cancer was higher for AMACR than for PTOV1. In conclusion, AMACR can be considered a more accurate marker than PTOV1 in the identification of HGPIN and of PCa. However, PTOV1 may aid in the diagnosis of PCa, at least to supplement AMACR as another positive marker of carcinoma and to potentially increase diagnostic accuracy.

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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

Cited by 48 publications

References 30 publications

PTOV1 Expression Predicts Prostate Cancer in Men with Isolated High-Grade Prostatic Intraepithelial Neoplasia in Needle Biopsy

PTOV1 Expression Predicts Prostate Cancer in Men with Isolated High-Grade Prostatic Intraepithelial Neoplasia in Needle Biopsy

Targeted Proteomic Analysis of 14-3-3ς, a p53 Effector Commonly Silenced in Cancer

Is There a Role for Prostate Tumour Overexpressed-1 in the Diagnosis of HGPIN and of Prostatic Adenocarcinoma? A Comparison with α-Methylacyl CoA Racemase

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