[The regulation of EKI-785 to the growth of U937 cell line].
OBJECTIVE
The aim of this study was to explore the expression of erbBs in U937, an acute monocyte leukemia cell line, and their impact on the growth of this cell line.


METHODS
Expression of erbBs was detected by RT-PCR and expression of erbB2 at protein level by Western blot. After U937 cells was treated with EKI-785, an irreversible specific inhibitor of erbBs, the growth was assessed by MTT and growth curve, apoptosis was detected by Annexin V-FITC Apoptosis Detection Kit, and signal pathway was detected by Western blot.


RESULTS
erbB2-4 were expressed in U937 cell line, but not erbB1. Especially, protein of erbB2 was expressed in this cell line. After treating with EKI-785, the growth of U937 cells was inhibited and early apoptosis was induced. Moreover, the Ras/MAPK and the PI3K/Akt signaling pathways were all blocked.


CONCLUSIONS
erbBs may play key roles in the development of some leukemia. Therefore, erbBs may become new targets of treatment to leukemia, and EKI-785 has a potency of clinic use to leukemia.
Yuan
Xiang-fei
XF
Institute of Hemotology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300020, China.
Lu
Shi-hong
SH
Feng
Yi
Y
Liu
Na
N
Song
Xin
X
Lu
Min
M
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells
D066246:ErbB Receptors; D020929:Mitogen-Activated Protein Kinase Kinases; D051057:Proto-Oncogene Proteins c-akt; D011799:Quinazolines; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C118029:CL 387785; C587689:ERBB4 protein, human