Inhibition of Akt/FOXO3a signaling by constitutively active FOXO3a suppresses growth of follicular thyroid cancer cell lines

Cancer Lett. 2012 Jan 1;314(1):34-40. doi: 10.1016/j.canlet.2011.09.010. Epub 2011 Sep 17.

Abstract

Akt-dependent FOXO3a cytoplasmic translocation is an important tumorigenic mechanism for escaping from apoptosis in cancer cells. In the present study, we examined whether non-phosphorylatable FOXO3a can inhibit cell growth of various follicular thyroid carcinoma (FTC) cell lines. Adenovirus carrying the FOXO3a-triple mutant (TM) sequence including point mutations at three Akt phosphorylation sites (Ad-FOXO3a-TM) was generated and transduced to the cells to mimic inhibition of Akt/FOXO3a signal. Transduction of Ad-FOXO3a-TM to FTC133 cells induced cell cycle arrest and apoptosis. Injection of Ad-FOXO3a-TM suppressed the growth of xenograft tumors in athymic mice. Consequently, our results indicate that gene therapy based on Ad-FOXO3a-TM has therapeutic potential for FTC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular
  • Adenoviridae / genetics
  • Apoptosis
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / genetics*
  • Genetic Therapy
  • Humans
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Signal Transduction / physiology
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / therapy*

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • Proto-Oncogene Proteins c-akt