Validation of HB-EGF and amphiregulin as targets for human cancer therapy.
Aberrant expression levels of epidermal growth factor receptor (EGFR) and its cognate ligands have been recognized as one of the causes of cancer progression. To investigate the validity of EGFR ligands as targets for cancer therapy, we examined the expression of EGFR ligands and in vitro anti-tumor effects of small interference RNA (siRNA) for EGFR ligands in various cancer cells. HB-EGF expression was dominantly elevated in ovarian, gastric, and breast cancer, melanoma and glioblastoma cells, whereas amphiregulin was primarily expressed in pancreatic, colon, and prostate cancer, renal cell carcinoma and cholangiocarcinoma cells. Transfection of siRNAs for HB-EGF or amphiregulin into these cells significantly increased the numbers of apoptotic cells with attenuation of EGFR and ERK activation. In lung cancer cells, any EGFR ligand was not recognized as a validated target for cancer therapy. These results suggest that HB-EGF and amphiregulin are promising targets for cancer therapy.
Yotsumoto
Fusanori
F
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Yagi
Hiroshi
H
Suzuki
Satoshi O
SO
Oki
Eiji
E
Tsujioka
Hiroshi
H
Hachisuga
Touru
T
Sonoda
Kenzo
K
Kawarabayashi
Tatsuhiko
T
Mekada
Eisuke
E
Miyamoto
Shingo
S
D066258:Amphiregulin; D045744:Cell Line, Tumor; D066255:EGF Family of Proteins; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D066258:Amphiregulin; D066255:EGF Family of Proteins; D066246:ErbB Receptors; D006023:Glycoproteins; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C587848:AREG protein, human; C587883:HBEGF protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human