Peroxisome proliferator-activated receptor gamma and retinoic acid receptor synergistically up-regulate the tumor suppressor PTEN in human promyeloid leukemia cells.
Peroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma 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 PPARgamma 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, PPARgamma and RAR play an important role in controlling the growth of leukemia cells via the up-regulation of PTEN.
Lee
Young-Rae
YR
Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Korea.
Yu
Hong-Nu
HN
Noh
Eun-Mi
EM
Kim
Jong-Suk
JS
Song
Eun-Kyung
EK
Han
Myung-Kwan
MK
Kim
Byeong-Soo
BS
Lee
Sung-Ho
SH
Park
Jinny
J
D002453:Cell Cycle / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D047495:PPAR gamma / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation
D047495:PPAR gamma; D018168:Receptors, Retinoic Acid; D045162:Thiazolidinediones; D014212:Tretinoin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C039671:ciglitazone