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 induced cell proliferation and signal
transduction in epidermal carcinoma cells A431
中文摘要
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-PD98059，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。
英文摘要
Epidermal growth factor (EGF) is a major mitogen for dermal fibroblasts. EGF induced fibroblasts proliferation by activating the EGF receptor (EGFR)-tyrosine kinase phosphorylation. In this study, we found EGF induced the significant 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 expression, however no change on the EGF- induced EGFR phosphorylated status. These results indicated that
phosphorylation of EGFR located upstream, and COX-2 located downstream of MAPK activation in EGF- induced signaling transduction. Investigating the inhibitory activities of structurally-related flavonoids including flavanone, 2'-OH
flavanone, 4'-OH flavanone, 6-OH flavanone, 7-OH flavanone, taxifolin, Wogonin and Fisetin on EGF- induced cellular proliferation, and intracellular signaling activation were involved in this study.
