表皮成長因子 ( Epidermal growth factor, EGF ) 是藉由受器的磷酸化傳 遞訊息來調控細胞生長和增生。在本研究中，我們發現表皮成長因子 (EGF) 能對表皮癌化細胞 (A431) 有促進增生的能力。實驗發現，於細 胞培養液中加入 10 ng/ml 的 EGF 能對 A431 細胞之受器產生時間依 循性的磷酸化表現， EGF 受器 (EGFR) 的磷酸化會誘導 MAPK 的活 化和 COX-2 蛋白質的表現。實驗中投予 MAPK 專一性抑制劑 -PD980 59 ，結果顯示 EGF 所誘導的 COX-2 蛋白質表現量減弱，但 EGF 所 誘導的 EGFR 的磷酸化卻沒有任何改變。這些結果指出， EGF 受器 磷酸化位於 MAPK 活化的上游位置 , 且 EGF 所誘導的 COX-2 蛋白質 表現是位於 MAPK 訊息傳遞的下游。本實驗以結構相似的類黃酮化 合物，包括 Flavonone,2'-OH flavanone 、 4'-OH flavanone、 6-OH flavanone 、 7-OH flavanone 、 taxifolin 、 wogonin and fisetin 來探討其抑制 EGF 所誘導的細胞增生和細胞訊息傳遞活化的能力。
表皮成長因子誘導細胞增生與訊息傳遞作用之研 究
Epidermal growth factor (EGF) is a major mitogen for dermal fibroblasts. EG F induced fibroblasts proliferation by activating the EGF receptor (EGFR)-tyr osine kinase phosphorylation. In this study, we found EGF induced the signifi cant proliferative effects in epidermal carcinoma cells A431. EGF receptors (EGFR) in A431 cells were time-dependently phosphorylated in the presence of EGF (10 ng /ml) in the culture medium. Upon EGF binding EGFR induced MAPK activation and cyclooxygenase 2 (COX-2) protein expression in A431 cells. PD98059, a MEK inhibitor, attenuated EGF- induced COX-2 protein ex pression, however no change on the EGF- induced EGFR phosphorylated stat us. These results indicated that phosphorylation of EGFR located upstream, a nd COX-2 located downstream of MAPK activation in EGF- induced signalin g transduction. Investigating the inhibitory activities of structurally-related fla vonoids including flavanone, 2'-OH flavanone, 4'-OH flavanone , 6-OH flavanone, 7-OH flavanone, taxifolin, Wogonin and Fisetin on EGF- i nduced cellular proliferation, and intracellular signaling activation were invol ved in this study.
Epidermal growth factor induced cell proliferati on and signal transduction in epidermal carcino ma cells A431
