Elimination of B-RAF in Oncogenic C-RAF-expressing Alveolar Epithelial Type II Cells Reduces MAPK Signal Intensity and Lung Tumor Growth

摘要: Tumors are often greatly dependent on signaling cascades promoting cell growth or survival and may become hypersensitive to inactivation of key components within these pathways. Ras RAF mutations found in human cancer confer constitutive activity molecules thereby converting them into an oncogenic state. dimerization is required for normal Ras-dependent activation the potential mutant RAFs. Here we describe a new mouse model lung tumor development investigate role B-RAF C-RAF-mediated adenoma initiation growth. Conditional elimination C-RAF BxB-expressing embryonic alveolar epithelial type II cells did not block formation. However, loss led significantly reduced The diminished upon was due proliferation absence senescence increased apoptosis. Furthermore, inhibited BxB-mediated mitogenic cascade. In line with data, mutation Ser-621 BxB abrogated vitro blocked ability activate MAPK Taken together data indicate that important factor tumorigenesis.