Androgen receptor promotes esophageal cancer cell migration and proliferation via matrix metalloproteinase 2

Tumour Biol. 2015 Aug;36(8):5859-64. doi: 10.1007/s13277-015-3257-x. Epub 2015 Feb 28.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. Androgen receptor (AR) plays an important role in many kinds of cancers. However, the molecular mechanisms of AR in ESCC are poorly characterized. In the present study, Western blot analysis and real-time quantitative PCR were performed to identify differentially expressed AR in 40 ESCC tissue samples, which revealed that the messenger RNA (mRNA) and protein expression of AR is upregulated in the ESCC tissue samples. AR overexpression induced increases in ESCC cell invasion and proliferation in vitro. Silencing of AR inhibited the proliferation of KYSE450 cells which have a relatively high level of AR, and the invasion of KYSE450 cells was distinctly suppressed. Furthermore, AR knockdown led to substantial reductions in matrix metalloproteinase 2 (MMP2) and p-AKT levels in ESCC cell lines, but no significant change in AKT and MMP9 expression. These results suggest that AR is involved in tumor progression, and thus, AR could represent selective targets for the molecularly targeted treatments of ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / biosynthesis
  • Neoplasm Invasiveness / genetics
  • Oncogene Protein v-akt / biosynthesis
  • RNA, Messenger / biosynthesis
  • RNA, Small Interfering
  • Receptors, Androgen / metabolism*

Substances

  • AR protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Androgen
  • Oncogene Protein v-akt
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9