RRC ID 69829
Author Ooki A, Yamashita K, Kikuchi S, Sakuramoto S, Katada N, Waraya M, Kawamata H, Nishimiya H, Nakamura K, Watanabe M.
Title Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer.
Journal BMC Cancer
Abstract BACKGROUND:Phosphatase of regenerating liver-3 (PRL-3) has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer.
METHODS:PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status.
RESULTS:PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (P = 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression.
CONCLUSIONS:We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression.
Volume 11
Pages 122
Published 2011-4-6
DOI 10.1186/1471-2407-11-122
PII 1471-2407-11-122
PMID 21466710
PMC PMC3080833
MeSH Apoptosis / drug effects Benzylidene Compounds / pharmacology* Cell Growth Processes / genetics Cell Line, Tumor Disease Progression Female Gene Amplification Gene Expression Regulation, Neoplastic / drug effects Gene Expression Regulation, Neoplastic / genetics Humans Male Neoplasm Invasiveness / genetics Neoplasm Metastasis / genetics Neoplasm Proteins / antagonists & inhibitors* Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Neoplasm Staging Protein Tyrosine Phosphatases / antagonists & inhibitors* Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism* RNA, Small Interfering / genetics Rhodanine / analogs & derivatives Rhodanine / pharmacology* Stomach Neoplasms / drug therapy Stomach Neoplasms / genetics Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Stomach Neoplasms / physiopathology
IF 3.15
Human and Animal Cells GCIY(RCB0555) Kato III(RCB2088) MKN74(RCB1002) NUGC-4(RCB1939)