Down-regulation of the expression of CCAAT/enhancer binding protein α gene in cervical squamous cell carcinoma

BMC Cancer. 2014 Jun 10:14:417. doi: 10.1186/1471-2407-14-417.

Abstract

Background: Cervical carcinoma is the second most common cancer and is an important cause of death in women worldwide. CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that regulate cellular differentiation and proliferation in a variety of tissues. However, the role of C/EBPα gene in cervical cancer is still not clear.

Methods: We investigated the expression of C/EBPα gene in cervical squamous cell carcinoma. C/EBPα mRNA level was measured by real-time quantitative RT-PCR in cervical cancer tissues and their adjacent normal tissues. C/EBPα protein level was measured by immunohistochemistry. Methylation in the promoter of C/EBPα gene was detected by MALDI TOF MassARRAY. We transfected HeLa cells with C/EBPα expression vector. C/EBPα expression in HeLa cells was examined and HeLa cell proliferation was measured by MTT assay and HeLa cells migration was analyzed by matrigel-coated transwell migration assays.

Results: There were significant difference in C/EBPα protein expression between chronic cervicitis and cervical carcinoma (P < 0.001). CEBPα mRNA level was significantly lower in cervical cancer tissues than in normal cervical tissues (P < 0.01). Methylation of the promoter of CEBPα gene in CpG 5, CpG-14.15, CpG-19.20 were significantly higher in cervical cancer than in normal cervical tissues (P < 0.05, P < 0.01, P < 0.05, respectively). CEBPα pcDNA3.1 construct transfected into HeLa cells inhibited cell proliferation and decreased cell migration.

Conclusions: Our results indicate that reduced C/EBPα gene expression may play a role in the development of cervical squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Protein-alpha / genetics*
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Movement
  • Cell Survival
  • DNA Methylation
  • Down-Regulation
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Neoplasm Grading
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transfection
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • RNA, Messenger