Retinoid X receptor alpha is highly phosphorylated in retinoic acid-resistant HL-60R cells and the combination of 9-cis retinoic acid plus MEK inhibitor induces apoptosis in the cells.
We examined the effects of 9-cis retinoic acid (RA) on the expression levels of retinoid X receptor alpha (RXR alpha) and its phosphorylated form (p-RXR alpha) in HL-60 and HL-60R cells. 9-cis RA reduced both RXR alpha and p-RXR alpha in HL-60 cells, but did neither in HL-60R cells. However, when the HL-60R cells were treated with the combination of 9-cis RA plus PD98059, MEK inhibitor, the p-RXR alpha and RXR alpha proteins all markedly decreased. Moreover, the combination of those agents induced apoptosis in HL-60R cells. Phosphorylation of RXR alpha might be associated with RA-resistance in HL-60R cells.
Kanemura
Nobuhiro
N
First Department of Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Tsurumi
Hisashi
H
Okuno
Masataka
M
Matsushima-Nishiwaki
Rie
R
Shimizu
Masahito
M
Moriwaki
Hisataka
H
D000077556:Alitretinoin; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047490:Retinoid X Receptor alpha / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009570:Nitriles; D047490:Retinoid X Receptor alpha; C113580:U 0126; D000077556:Alitretinoin; D014212:Tretinoin; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one