In vitro and in vivo evidence of metallopanstimulin-1 in gastric cancer progression and tumorigenicity

Clin Cancer Res. 2006 Aug 15;12(16):4965-73. doi: 10.1158/1078-0432.CCR-05-2316.

Abstract

Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Blotting, Western / methods
  • Cell Line, Tumor
  • Disease Progression
  • Humans
  • Male
  • Metalloproteins / biosynthesis
  • Metalloproteins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics*
  • Rabbits
  • Ribosomal Proteins / biosynthesis
  • Ribosomal Proteins / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transfection
  • Transplantation, Heterologous
  • Tumor Stem Cell Assay / methods

Substances

  • Metalloproteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • RPS27 protein, human
  • Ribosomal Proteins