Journal
CLINICAL CANCER RESEARCH
Volume 11, Issue 19, Pages 6835-6839Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-04-2357
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Purpose: The PRL-3 phosphatase has been found expressed at higher levels in metastasis than in primary tumors,of patients with colorectal cancer. In the present study, we evaluated the expression of PRL-3 in ovarian cancer tissue and its role in ovarian cancer cell growth. Experimental Design: PRL-3 phosphatase expression was evaluated in 84 ovarian tumor samples. PRL-3 expression has been knocked down using Specific small interfering RNAs to determine its role in ovarian cancer cell growth in vitro. Results: In ovarian cancers, PRL-3 expression correlates with disease progression, being higher in advanced (stage III) than in early (stage 1) tumors. In situ measurements of PRL-3 expression showed that it was confined to the epithelial neoplastic cells. The molecular mechanism underlying PRL-3 overexpression in ovarian cancers is independent from amplification of the corresponding genomic locus. Ovarian cancer cells growing in culture have high levels of expression of this phosphatase. PRL-3-specific knockdown using small interfering RNA severely impaired-the growth of cells-without affecting the expression of the closely related homologue PRL-1 Intriguingly, the growth of human colon carcinoma cells expressing lower levels of the PRL-3 was not affected by the, PRL-3 knockdown. Conclusions: Altogether, these results show that PRL-3 expression is associated with ovarian cancer, progression and point to a key role for this phosphatase in the control of ovarian cancer cells growth. This strongly suggests that PRL-3 should be considered as a target-for the discovery of new anticancer agents to be tested against this malignancy.
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