Potential Dual Role of Activating Transcription Factor 3 in Colorectal Cancer

Anticancer Res. 2016 Feb;36(2):509-16.

Abstract

Background/aim: Activating transcription factor 3 (ATF3) is a member of the ATF/CREB transcription factor family and has been proposed as a molecular target for cancer therapy. The present study was undertaken in order to investigate whether ATF3 influences cancer-related phenotypes in colorectal cancer.

Materials and methods: ATF3 was overexpressed in human colorectal cancer cells and the effects of ATF3 on apoptosis, cell cycle, cell migration and epithelial mesenchymal transition (EMT) were investigated. B-cell lymphoma-2 (Bcl-2) promoter was cloned and used for luciferase assay in cells transfected with control or ATF3 expression vector.

Results: ATF3 down-regulated the expression of Bcl-2 and promoter activity of the Bcl-2 gene. ATF3 increased collective cell migration and expression of cluster of differentiation 44 (CD44) and decreased retinoblastoma (Rb) expression. In addition, ATF3 down-regulated EMT-inducing transcription factors and β-catenin.

Conclusion: ATF3 may play a dichotomous role in apoptosis and metastasis in human colorectal cancer cells.

Keywords: Activating transcription factor 3; Bcl-2; apoptosis; colorectal cancer; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / genetics
  • Activating Transcription Factor 3 / metabolism*
  • Apoptosis*
  • Blotting, Western
  • Cell Cycle
  • Cell Movement*
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • ATF3 protein, human
  • Activating Transcription Factor 3
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger