Filamin A regulates MMP-9 expression and suppresses prostate cancer cell migration and invasion

Tumour Biol. 2014 Apr;35(4):3819-26. doi: 10.1007/s13277-013-1504-6. Epub 2014 Jan 5.

Abstract

This study aims to analyze the expression and clinical significance of Filamin A (FLNA) in prostate carcinoma and the biological effect in its cell line by FLNA overexpression. Immunohistochemistry and Western blot were used to analyze FLNA protein expression in 68 cases of prostate cancer and 37 cases of normal tissues to study the influence of the upregulated expression of FLNA that might be found on PC-3 cell biological effect. In the immunohistochemical analysis, the level of FLNA protein expression was found to be significantly lower in prostate cancer tissue than in normal tissues (P < 0.05). In the Western blot analysis, the relative amount of FLNA protein in prostate cancer tissue was found to be significantly lower than in normal tissues (P < 0.05). The level of FLNA protein expression was not correlated with age and PSA concentration (P > 0.05), but it was correlated with T stages, lymph node metastasis, clinic stage, and Gleason score (P < 0.05). The result of biological function showed that PC-3 cell transfected FLNA had a lower survival fraction, a significant decrease in migration and invasion, and a lower matrix metallopeptidase 9 (MMP-9) protein expression compared with PC-3 cell untransfected FLNA (P < 0.05). FLNA expression decreased in prostate cancer and correlated significantly with T stages, lymph node metastasis, clinic stage, and Gleason score, suggesting that FLNA may play important roles as a negative regulator to prostate cancer PC-3 cell by promoting the degradation of MMP-9.

MeSH terms

  • Aged
  • Cell Movement*
  • Filamins / analysis
  • Filamins / genetics
  • Filamins / physiology*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology*

Substances

  • Filamins
  • MMP9 protein, human
  • Matrix Metalloproteinase 9