Activation of androgen receptor induces ID1 and promotes hepatocellular carcinoma cell migration and invasion

Mol Oncol. 2012 Oct;6(5):507-15. doi: 10.1016/j.molonc.2012.06.005. Epub 2012 Jul 5.

Abstract

Androgen receptor (AR) activity is associated with cancer development and progression. In hepatocellular carcinoma (HCC), AR contributes to HCC incidence, but the role of AR in HCC cell migration and invasion remains largely unknown. In this study, we found that AR was expressed at high levels in a subgroup of HCC cell lines with high metastatic potential. Experiments using lentiviral overexpression or small hairpin RNA knockdown of AR as well as activation of AR by its ligand indicated that AR activation promoted HCC cell migration and invasion. We also found that AR activation enhanced the expression of a metastasis-promoting gene, ID1, which led to increased HCC cell migration and invasion. An AR antagonist was able to block this process, suggesting that AR activation in AR-positive HCC may be therapeutically inhibited as a potential intervention strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitor of Differentiation Protein 1 / genetics*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • RNA, Messenger / genetics
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Up-Regulation

Substances

  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • RNA, Messenger
  • Receptors, Androgen