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 sy...

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Bibliographic Details
Published in:International journal of hematology 2007-04, Vol.85 (3), p.231-237
Main Authors: Lee, Young-Rae, Yu, Hong-Nu, Noh, Eun-Mi, Kim, Jong-Suk, Song, Eun-Kyung, Han, Myung-Kwan, Kim, Byeong-Soo, Lee, Sung-Ho, Park, Jinny
Format: Article
Language:English
Subjects:
Cell Cycle - physiology
HL-60 Cells
Humans
PPAR gamma - physiology
PTEN Phosphohydrolase - metabolism
Receptors, Retinoic Acid - physiology
Thiazolidinediones - pharmacology
Tretinoin - pharmacology
Up-Regulation
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Summary: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.
ISSN:0925-5710
1865-3774
DOI:10.1532/IJH97.A30615