Molecular mechanisms of cellular proliferation in acute myelogenous leukemia by leptin.
Leptin acts as a growth factor in normal cells as well as in various types of cancer cells. We investigated the effects of leptin on human acute myelogenous leukemia (AML) cells. Leptin stimulated the proliferation of HEL cells through the phosphorylation of STAT3 and ERK1/2. The blocking of STAT3 phosphorylation with the specific inhibitor, AG490, significantly reduced leptin-induced ERK1/2 phosphorylation and cellular proliferation, whereas the blocking of ERK1/2 activation by the specific ERK1/2 inhibitor, PD98059, did not affect the STAT3 phosphorylation or leptin-induced proliferation in HEL cells. Furthermore, knockdown of leptin receptor (OB-R) expression with stealth RNA interference (RNAi) reduced the leptin-induced proliferation of HEL cells and also significantly attenuated leptin-induced STAT3 and ERK1/2 activation. These results suggest that leptin promotes AML cell growth by activating STAT3 and MAPK, although not directly dependent on ERK.
Kim
Ju Young
JY
Laboratory of Hematopoiesis and Hematologic Malignancy, Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Korea.
Park
Hyun Ki
HK
Yoon
Jin Sun
JS
Kim
Seo Ju
SJ
Kim
Eun Shil
ES
Song
Sung Heon
SH
Choi
Jung Hye
JH
Kim
Byoung Kook
BK
Park
Byoung Bae
BB
Lee
Young Yiul
YY
D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D020738:Leptin / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology
D005419:Flavonoids; C515448:LEPR protein, human; D020738:Leptin; D047428:Protein Kinase Inhibitors; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one