K-ras 변이가 있는 췌장암세포주에서 Mitogen Activated Protein Kinase와 PI 3-kinase가 세포증식에 미치는 역할

Background/Aims: K-ras mutation is considered to be important for the development and proliferation of pancreatic cancer. After activation of Ras protein, several cytoplasmic protein kinases, such as the mitogen activated protein kinase (MAPK) signaling cascade and PI 3-kinase, are sequentially stimulated. The aim of this study was to examine the role of MAPK and PI 3-kinase on cellular proliferation of pancreatic cancer cell lines with K-ras mutation. Methods: MiaPaCa-2 and Panc-1 cell lines were cultured and stimulated with growth factors such as fetal bovine serum (FBS) and epidermal growth factor (EGF). The cell proliferation was measured by 3H thymidine incorporation assay. MAPK/extracellular signal regulated kinase (ERK) activating kinase (MEK) inhibitor (PD098059) or PI 3- kinase inhibitor (wortmannin) was added in media and their effects on proliferation were examined. The activity of ERK was measured by immunoblotting assay. Results: FBS stimulated cell proliferation dose-dependently in both cell lines but EGF did not. PD098059 blocked dose-dependently the cell proliferation but wortmannin did not. The activities of ERK were increased by both FBS and EGF and blocked only by PD098059. Conclusions: MAPK kinase signal transduction pathway from MEK to ERK plays an important role in the stimulation of proliferation in pancreatic cancer cell lines with K-ras mutation. (Kor J Gastroenterol 2000;36:372 - 382)