| セッション情報 |
International Forum 1(Gastrointestinal tract) 1.Prostaglandins and gastrointestinal mucosa
|
| タイトル |
IF1-1-II (Plenary presentation) Epinephrine stimulates esophageal squamous-cell carcinoma cell proliferation via β-adrenoceptor-dependent transactivation of extracellular signal-regulated kinase/cyclooxgenase-2 pathway
|
| 演者 |
Xuan Liu（Beijing Friendship Hospital^1） |
| 共同演者 |
William K.K.Wu, Helen P.S.Wong（Departments of PharmacologyThe University of Hong KongHong Kong SARChina^4）, Emily K.K.Tai（Departments of PharmacologyThe University of Hong KongHong Kong SARChina^4）, Le Yu（Departments of PharmacologyThe Chinese University of Hong KongHong Kong SARChina^3）, Wallace H.L.So（Departments of PharmacologyThe University of Hong KongHong Kong SARChina^4）, Joseph J.Y.Sung（Departments of Medicine & TherapeuticsThe Chinese University of Hong KongHong Kong SARChina^2）, Gopesh Srivastava（Departments of PathologyThe University of Hong KongHong Kong SARChina^5）, Shu T.Zhang（Beijing Digestive Diseases CenterCapital Medical UniversityBeijingChina^6）, Chi H.Cho（Departments of PharmacologyThe Chinese University of Hong KongHong Kong SARChina^3） |
| 抄録 |
Esophageal cancer is one of the leading causes of cancer-related death in the world． lt is suggested that B-adrenoceptor is involved in the control of cell proliferationbut its role in the pathogenesis of esophagealcancer remains unknownWe therefore studied the role of P-adrenergic signaling in the regulation of thegrowth of an esophageal squamous-cell carcinoma cell line HKESC-1． Results showed that both the tran-scripts and proteins of Pi- and P2-adrenoceptors were expressed in HKESC-1 cells． Stimulation of B-adrenoceptors with epinephrine significantly increased HKESC-1 cell proliferation accompanied by eleva-tion of intracellular cyclic AMP levelswhich were abolished by Pi- or P2-selective antagonistsEpineph-rine also increased extracellular signal-regulated kinase-1／2 （ERK I／2） phosphorylation as well as cy-clooxygenase-2（COX-2）and cytosolic phospholipase A、 expressionwhich were blocked byβ1-orβ-se-lective antagonists． ln additionepinephrine increased cyclin D icyclin E 2cyclin-dependent kinase（CDK） -4CDK-6and E2F-1 expression as well as retinoblastoma protein phosphorylation at Ser807／811all of which were abrogated by Bi-adrenoceptor antagonist． Furthermoreepinephrine increased the ex-pression of vascular endothelial growth factor （VEGF）VEGF receptor （VEGFR）-1 and -2 in HKESC-1cells in a P2-adrenoceptor-mitogen-activated protein kinase／ERK kinase （MEK） -and COX-2-depend-ent manner． MEK or COX-2 inhibitor also significantly inhibited HKESC-1 cell proliferation induced byepinephrine． To concludewe demonstrate for the firsttime that epinephrine stimulated esophagealsquamous-cell carcinoma cell proliferation via B-adrenoceptor-dependent transactivation of ERK／COX-2signaling pathway． This novel finding may shed new light on the understanding of S-adrenoceptor signal-ing in the control of cancer cell growth． |
| 索引用語 |
|
