Constitutive suppression of PRL-3 inhibits invasion and proliferation of gastric cancer cell in vitro and in vivo.
OBJECTIVE
Overexpression of phosphatase of regenerating liver-3 (PRL-3) has been implicated in tumor progression and metastasis of gastric carcinoma. Here we examined what alterations occur in the phenotype of gastric cancer cells in vitro and in vivo when PRL-3 expression is knocked down.


METHODS
We constructed a small interfering RNA (siRNA)-expressing vector which stably interfered with PRL-3 expression and was transfected into SH101-P4 cells, which express the highest PRL-3 mRNA levels among 13 gastric cancer cell lines. The new SH101-P4 subclones, in which PRL-3 was stably reduced, were established and their in vitro growth, motility and abilities of liver metastasis from the injected spleen were analyzed in vivo.


RESULTS
PRL-3 knockdown effectively suppressed invasion and growth of SH101-P4 cells in vitro. Liver metastasis in vivo was significantly decreased when PRL-3 expression was suppressed. The primary tumor size in the injected spleen tended to be smaller in PRL-3 knockdown clones than in the controls. These findings suggest that PRL-3 expression may contribute not only to the establishment of metastasis but also to the growth of primary foci of human gastric cancer. Therefore, PRL-3 may be one of the target molecules in gastric cancer therapy.
Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yasuko
Y
Matsukawa
Shuho
S
Semba
Hirotaka
H
Kato
Yu-Ichiro
Y
Koma
Kazuyoshi
K
Yanagihara
Hiroshi
H
Yokozaki
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
D009363:Neoplasm Proteins; D012333:RNA, Messenger; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases