International Journal of Hematology

, Volume 85, Issue 3, pp 231–237 | Cite as

Peroxisome Proliferator-Activated Receptor γ and Retinoic Acid Receptor Synergistically Up-Regulate the Tumor Suppressor PTEN in Human Promyeloid Leukemia Cells

  • Young-Rae Lee
  • Hong-Nu Yu
  • Eun-Mi Noh
  • Jong-Suk Kim
  • Eun-Kyung Song
  • Myung-Kwan Han
  • Byeong-Soo Kim
  • Sung-Ho Lee
  • Jinny Parkd


Peroxisome proliferator-activated receptor γ (PPARγ) and retinoic acid receptors (RARs) have been a focus in chemotherapy for human cancers. The tumor suppressor PTEN plays a pivotal role in the growth of human cancer cells. We investigated whether costimulation of PPARγ and RAR could synergistically up-regulate PTEN in human leukemia cells and consequently potentiate the inhibition of growth and cell cycle progression of these cells. We found that overexpression of PTEN with the adenoviral vector Ad/PTEN caused growth arrest at the G1 phase of the cell cycle of HL-60 cells. HL-60 cells treated with either a PPARγ ligand (ciglitazone) or a RAR ligand(all-trans retinoic acid [ATRA]) up-regulated PTEN in HL-60 cells. The 2 compounds in combination showed synergistic effects on PTEN expression at the protein and messenger RNA levels. Moreover, the combination of ciglitazone and ATRA synergistically reduced cell growth rates and cell cycle arrest at the G1 phase. Our results suggest that, PPARγ and RAR play an important role in controlling the growth of leukemia cells via the up-regulation of PTEN.

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Copyright information

© The Japanese Society of Hematology 2007

Authors and Affiliations

  • Young-Rae Lee
    • 1
  • Hong-Nu Yu
    • 1
  • Eun-Mi Noh
    • 1
  • Jong-Suk Kim
    • 1
  • Eun-Kyung Song
    • 1
  • Myung-Kwan Han
    • 2
  • Byeong-Soo Kim
    • 3
  • Sung-Ho Lee
    • 3
  • Jinny Parkd
    • 4
  1. 1.Department of BiochemistryChonbuk National University Medical SchoolJeonjuKorea
  2. 2.Department of Microbiology & ImmunologyChonbuk National University Medical SchoolJeonjuKorea
  3. 3.Department of Companion and Laboratory Animal ScienceKongju National UniversityYesanKorea
  4. 4.Division of Hematology/OncologyGachon University Medical CenterInchonKorea

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