CIAPIN1 inhibits gastric cancer cell proliferation and cell cycle progression by downregulating CyclinD1 and upregulating P27

Cancer Biol Ther. 2007 Oct;6(10):1539-45. doi: 10.4161/cbt.6.10.4684.

Abstract

CIAPIN1, a newly identified apoptosis-related molecule, was found to be downregulated in human gastric cancer tissues as compared to the matched adjacent nonneoplastic tissues. In this study, we investigated the effect of CIAPIN1 on in vitro and in vivo proliferation of gastric cancer cells. Ectopic expression and knockdown of CIAPIN1 in gastric cancer cells SGC7901 and MKN45 were achieved by transduction with recombinant adenoviruses expressing human CIAPIN1 (Ad-CIAPIN1) and human CIAPIN1-specific small interference RNA (Ad-CIAPIN1 siRNA). Gastric cancer cells with upregulated expression of CIAPIN1 exhibited significantly decreased proliferation, while cellswith downregulated CIAPIN1 expression showed significantly quicker growth rate as compared with their respective controls in both in vitro and in vivo tests. Also, CIAPIN1suppressed colony formation of SGC7901 and MKN45 cells in soft agar cloning test.Furthermore, cell cycle distribution analysis revealed that CIAPIN1 induced cell cycle arrest at G1/S phase. Downregulation of CyclyinD1 and upregulation of P27 might contribute, at least in part, to this altered cell cycle distribution. This study demonstrates that CIAPIN1 is a suppressor of gastric cancer cell proliferation and suggests CIAPIN1might play an important role in the development of human gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Down-Regulation
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • RNA, Small Interfering / pharmacology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Transduction, Genetic
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*
  • Up-Regulation

Substances

  • CIAPIN1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27