In vitro and in vivo evidence of metallopanstimulin-1 in gastric cancer progression and tumorigenicity.
OBJECTIVE
The metallopanstimulin-1 (MPS-1) gene is a growth factor-inducible gene, which is highly expressed in many human cancers and may be involved in the progression towards tumor malignancy. However, it is unclear whether MPS-1 plays any role in gastric cancer development or progression. Our studies were designed to clarify the MPS-1 expression pattern and to explore its potential role in gastric cancer.


METHODS
The expression pattern of MPS-1 was determined in primary gastric cancer specimens and gastric cancer cell lines via immunohistochemistry and Western blotting. To investigate the functional significance of MPS-1 expression, three small interfering RNA (siRNA) expression plasmids were constructed and transfected into gastric cancer cell line SGC7901. The stable cell lines transfected with the siRNA targeting MPS-1 mRNA plasmids were selected and the biological features of these cells were examined.


RESULTS
MPS-1 was overexpressed in 86% of the gastric cancer tissues and all gastric cancer cells. In addition, MPS-1 expression was significantly increased and corresponded with the tumor-node-metastasis clinical stage, and was significantly higher in the late stage (P < 0.01). The MPS-1 expression level was significantly decreased in the transfected cells with MPS-1-specific siRNA expression plasmid pRNAT-133. Furthermore, the stable transfected cancer cells exhibited an increase in the incidence of spontaneous apoptosis and a decrease in growth ability and tumorigenicity in nude mice.


CONCLUSIONS
These results provide strong evidence that MPS-1 plays an important role in gastric cancer cell proliferation and development, and suggests that MPS-1 is a promising target for gastric cancer treatment.
Wang
Yun-Wei
YW
Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Qu
Ying
Y
Li
Jian-Fang
JF
Chen
Xue-Hua
XH
Liu
Bing-Ya
BY
Gu
Qin-Long
QL
Zhu
Zheng-Gang
ZG
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D008297:Male; D008667:Metalloproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D011817:Rabbits; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay / Q000379:methods
D008667:Metalloproteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C083686:RPS27 protein, human; D012269:Ribosomal Proteins