PRL-3 phosphatase is implicated in ovarian cancer growth.
OBJECTIVE
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.


METHODS
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.
Polato
Federica
F
Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Codegoni
Annamaria
A
Fruscio
Robert
R
Perego
Patrizia
P
Mangioni
Costantino
C
Saha
Saurabh
S
Bardelli
Alberto
A
Broggini
Massimo
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D017403:In Situ Hybridization; D009363:Neoplasm Proteins / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000201:enzymology*; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012313:RNA; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases