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and Gastrointestinal Tumors Course Websites ckit和胃肠道肿瘤的课程教学网站课件
C-Kit and Gastrointestinal Stromal Tumors By Jessica Danielle Stewart The Story of KIT is a Familiar One (Hint: Think Src and Ras) A Familiar Story…. Transmembrane tyrosine kinase receptor Stem cell factor (SCF) Related to PDGFR α and β, CSF1R, and FLT3 First discovered in felines KIT and the Cell Cell proliferation Cell adhesion Cell Differentiation Apoptosis KIT and the Cell “… expressed at high levels in hematopoietic stem cells, mast cells, melanocytic cells, germ cells, and interstitial cells of Cajal (ICC)”. – Heinrich, Michael C, et al. Gastrointestinal Stromal Tumors Gastrointestinal Stromal Tumors (GISTs) Rare Most frequent mesenchymal tumors of the digestive tract What Happens with KIT and Mice? KIT and Mice Models (disruption of KIT) absence of functional ICC aperistalsis of the gut anemia white coat color sterility KIT and Mouse Models (gain of function) “Sommer et al produced a mouse model for familial GISTs… patch hyperplasia of ICCs is evident within the myenteric plexus for the entire GI tract, and neoplastic lesions indistinguishable from human GISTS were observed…”– Kitamura, et al. KIT and Mouse Models (gain of function) “Sommer et al produced a mouse model for familial GISTs… patch hyperplasia of ICCs is evident within the myenteric plexus for the entire GI tract, and neoplastic lesions indistinguishable from human GISTS were observed…”– Kitamura, et al. KIT and Cancer (GISTs) KIT is an oncogene Usually receptor dimerization occur in the absence of a ligand Might be one of earliest transforming events in GISTs Involved in small cell lung carcinomas, melanomas, seminomas, and gastrointestinal stromal tumors KIT and Cancer (GISTs) Mutations affect the kinase and the regulatory regions Different mutations lead to different phenotypes KIT and Cancer (GISTs) “… the exact signaling pathways activated by the mutant KIT differ from those activated by normal KIT. We believe that is also the case in GISTs where the signaling cascades governed by
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