Wnt/beta-catenin signaling pathway may regulate cell cycle and expression of cyclin A and cyclin E protein in hepatocellular carcinoma cells

Cell Cycle. 2009 May 15;8(10):1567-70. doi: 10.4161/cc.8.10.8489. Epub 2009 May 19.

Abstract

Wnt/beta-catenin signaling pathway and cell cycle play the key roles during the genesis and development of hepatocellular carcinoma (HCC). The cytoplasmic protein beta-catenin is a multifunctional protein and a central molecule in the Wnt signaling pathway. Cell cycle is regulated by a a series of regulatory factors. Current researches indicated that expression of cyclin D1 and c-myc decreased after silencing beta-catenin gene in HCC, but it is unclear if other cyclins are affected. To determine the relation, small interference RNA(siRNA) against beta-catenin was transfected into HCC cell line HepG(2), and cell cycle and cyclin A and cyclin E protein expression were detected. We demonstrated that cell cycle was arrested in G(0)/G(1) at 72 h after the transfection and with the time passing, the cell cycle began to transfer from G(0)/G(1) to G(2)/M through S and had a trend to revert at 96 h. In addition, beta-catenin protein expression was decreased at both 72 and 96 h, although the level was slightly higher at 96 h than that at 72 h. However, cyclin A and cyclin E protein expression increased at 72 h and decreased at 96 h. These findings suggest that silencing beta-catenin gene may induce the changes of cell cycle and cyclin A and cyclin E expression. Wnt/beta-catenin signaling pathway probably takes part in the genesis and development of HCC through regulating cell cycle and the expression of cyclin A and cyclin E.

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Cell Cycle*
  • Cell Line, Tumor
  • Cyclin A / metabolism*
  • Cyclin E / metabolism*
  • Humans
  • Liver Neoplasms / metabolism*
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Cyclin A
  • Cyclin E
  • RNA, Small Interfering
  • Wnt Proteins
  • beta Catenin