Induction of apoptosis by an inhibitor of EGFR in neuroblastoma cells.
We aimed to examine the expression of EGFR in neuroblastoma tissues and to investigate the antitumor activity of a selective EGFR-tyrosine kinase inhibitor, gefitinib, on neuroblastoma. The expression of EGFR was detected in each of two tumor tissues by immunohistochemistry and eight of 10 cell lines by Western blotting. Gefitinib inhibited EGFR-phosphorylation and in vitro cell growth (IC(50): approximately 1.2 microM), and a high concentration of gefitinib (20-30 microM) induced apoptosis in vitro. This is the first report that EGFR protein is expressed on the cell surface in neuroblastoma tissues and in cell lines. We also demonstrated an EGFR inhibitor induced apoptosis on neuroblastoma cells. Our results suggest the feasibility of targeting EGFR as a novel strategy against neuroblastoma.
Tamura
Shinichi
S
Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Shinichi.Tamura@ma1.seikyou.ne.jp
Hosoi
Hajime
H
Kuwahara
Yasumichi
Y
Kikuchi
Ken
K
Otabe
Osamu
O
Izumi
Moriatsu
M
Tsuchiya
Kunihiko
K
Iehara
Tomoko
T
Gotoh
Takahiro
T
Sugimoto
Tohru
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077156:Gefitinib; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011799:Quinazolines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib