Thyrotroph embryonic factor is downregulated in bladder cancer and suppresses proliferation and tumorigenesis via the AKT/FOXOs signalling pathway

Cell Prolif. 2019 Mar;52(2):e12560. doi: 10.1111/cpr.12560. Epub 2018 Dec 4.

Abstract

Objectives: Thyrotroph embryonic factor (TEF) plays an important role in several different processes in normal human cells; however, its function in malignant cells has not been fully elucidated.

Materials and methods: The mRNA levels of TEF in 408 bladder cancer (BC) samples from the Cancer Genome Atlas (TCGA) database were analysed in depth. Next, the expression of TEF in 7 BC cell lines was compared to that in normal bladder epithelial cells. The cell count, colony formation and anchorage-independent growth assays as well as a nude mouse xenograft model were utilized to examine the effects of TEF on proliferation and tumorigenesis. Immunofluorescence staining, flow cytometry analysis and treatment with an AKT inhibitor were performed to explore the molecular regulation mechanisms of TEF in BC.

Results: Analysis of TCGA data indicated that TEF mRNA was decreased in BC samples compared to that in normal bladder epithelial cells and correlated with the poor survival of BC patients. Additional experiments verified that the mRNA and protein expression of TEF were significantly decreased in BC cells compared to that in normal bladder epithelial cells. Upregulation of TEF expression significantly retarded BC cell growth by inhibiting the G1/S transition via regulating AKT/FOXOs signalling.

Conclusion: Our results suggest that TEF might play an important role in suppressing BC cells proliferation and tumorigenesis.

Keywords: FOXO; G1/S; TEF; bladder cancer; proliferation.

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation*
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Inbred NOD
  • Mice, Nude
  • Mice, SCID
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Survival Analysis
  • Urinary Bladder Neoplasms / epidemiology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Forkhead Transcription Factors
  • TEF protein, human
  • Tef protein, mouse
  • Proto-Oncogene Proteins c-akt