A MOUSE MODEL FOR ASSESSING THE EFFECTS OF CHECKPOINT DYSFUNCTION ON KRAS-INDUCED LUNG TUMORIGENESIS

摘要

Kras activating mutations occur in many human neoplasms, including lung adenocarcinomas, and the majority of spontaneous and chemically-induced murine lung tumors. Alterations in Ras family genes have also been implicated in canine and feline neoplasms (e.g. lung and pancreatic adenocarcinomas, leukemias, and mammary tumors). Oncogenic signals such as this are counteracted in part by DNA damage checkpoint pathways, which trigger cell cycle arrest and subsequent repair, senescence, or apoptosis. The Atr signaling pathway is one of the primary DNA damage checkpoint mechanisms in mammalian cells, but its tumor suppressor functions are poorly understood. The objective of this study was to evaluate how lung-specific inactivation of Husl, an essential component of the Atr checkpoint pathway, affects Kras-induced lung tumorigenesis in mice.