Gankyrin promotes the proliferation of human pancreatic cancer

Cancer Lett. 2010 Nov 1;297(1):9-17. doi: 10.1016/j.canlet.2010.04.019. Epub 2010 May 18.

Abstract

Previous studies in our laboratory have suggested that gankyrin expression is correlated with a malignant phenotype in colorectal cancer. Here, we investigated the possible role of gankyrin in pancreatic carcinogenesis. Gankyrin expression was significantly increased in pancreatic cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo. Suppression of gankyrin downregulated cyclin A, cyclin D1, cyclin E, CDK2, CDK4, PCNA and p-Rb but upregulated p27, Rb and p53. However, gankyrin overexpression led to opposite results. Thus, gankyrin could enhance pancreatic cancer cell proliferation by promoting cell cycle progression and p53 degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cyclin A / metabolism
  • Cyclin D1 / metabolism
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Staging
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Phosphorylation
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA Interference
  • Retinoblastoma Protein / metabolism
  • Time Factors
  • Transfection
  • Tumor Burden
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation

Substances

  • CCND1 protein, human
  • Cyclin A
  • Cyclin E
  • PSMD10 protein, human
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins
  • Retinoblastoma Protein
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • CDK2 protein, human
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Proteasome Endopeptidase Complex