[Epidermal growth factor-mediated NF-kappaB activation promotes uPA expression and invasiveness in pancreatic cancer cells].
OBJECTIVE
To determine the effect of EGF on the invasiveness of pancreatic cancer cells and its related regulatory mechanism.


METHODS
The effects of EGF on the proliferation, adhesion and invasion of pancreatic cancer cells were detected by WST-1 proliferation assay, adhesion assay and invasive assay. The expression of uPA was assayed by Western blot and RT-PCR. The activity of NF-kappaB was examined by EMSA.


RESULTS
EGF significantly increased the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion. Increased invasiveness was associated with the induction of uPA at both mRNA and protein levels. Furthermore, EGF stimulated the NF-kappaB binding activity, and pretreatment of cells with a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated EGF-induced NF-kappaB activation. Subsequently, the EGF-induced uPA expression and invasiveness were also inhibited by NF-kappaB inhibitor.


CONCLUSIONS
Our findings indicated that NF-kappaB-mediated up-regulation of uPA expression is responsible for EGF-induced invasiveness in pancreatic cancer cells, and implicate that such anti-NF-kappaB therapy with NF-kappaB inhibitors may contribute to the reduction of invasiveness of pancreatic cancer.
Zhang
Hao
H
Department of Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Liu
Xiao-Fang
XF
Li
Yu-Ji
YJ
Zhou
Jian-Ping
JP
Kong
Fan-Min
FM
Dong
Ming
M
D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D004815:Epidermal Growth Factor; D014568:Urokinase-Type Plasminogen Activator