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Human Cancer Biology |
Authors' Affiliations: 1 Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy; 2 Ospedale San Gerardo, Monza, Italy; 3 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; and 4 Oncogenomic Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Turin,Italy and IFOM, Milan, Italy
Requests for reprints: Massimo Broggini, Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche, "Mario Negri," via Eritrea 62, 20157 Milan, Italy. Phone: 39-2-39014585; Fax: 39-2-3546277; E-mail: broggini{at}marionegri.it or Alberto Bardelli, Oncogenomic Center, Institute for Cancer Research and Treatment, University of Torino Medical School, SP 142, Km. 3.95, 10060 Candiolo, Turin, Italy. E-mail: a.bardelli{at}ircc.it.
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 I) 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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