An antiproliferative gene FLNA regulates migration and invasion of gastric carcinoma cell in vitro and its clinical significance

Tumour Biol. 2014 Mar;35(3):2641-8. doi: 10.1007/s13277-013-1347-1. Epub 2013 Nov 16.

Abstract

This study aimed to analyze the expression and clinical significance of filamin A (FLNA) in gastric carcinoma and the biological effect in its cell line by FLNA overexpression. Immunohistochemistry and western blot were used to analyze FLNA protein expression in 47 cases of gastric cancer and 47 cases of normal tissues to study the relationship between FLNA expression and clinical factors. FLNA lentiviral vector and empty vector were respectively transfected into gastric cancer SGC-7901 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to detect the mRNA level and protein of FLNA. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and migration and invasion assays were also conducted to determine the influence of the upregulated expression of FLNA that might be found on SGC-7901 cell biological effect. Immunohistochemistry: The level of FLNA protein expression was found to be significantly lower in gastric cancer tissue than normal tissues (P < 0.05). Western blot: The relative amount of FLNA protein in gastric 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 gender, age, and tumor invasion (P > 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grade (P < 0.05). Loss of FLNA expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result of biological function showed that SGC-7901 cell transfected FLNA had a lower survival fraction, significant decrease in migration and invasion, and lower matrix metallopeptidase 9 (MMP-9) protein expression compared with SGC-7901 cell untransfected FLNA (P < 0.05). FLNA expression decreased in gastric cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that FLNA may play important roles as a negative regulator to gastric cancer SGC-7901 cell by promoting degradation of MMP-9.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Female
  • Filamins / biosynthesis*
  • Filamins / genetics
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Transfection
  • Young Adult

Substances

  • Biomarkers, Tumor
  • FLNA protein, human
  • Filamins