Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer

摘要: Human lung adenocarcinoma, the most prevalent form of cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with initiation adenocarcinomas, but K-ras-independent mechanisms may also initiate tumors. Here, we find that runt-related transcription factor Runx3 essential for normal murine development and a tumor suppressor prevents adenocarcinoma. Runx3-/- mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, bronchioli impaired differentiation, as evidenced accumulation epithelial cells containing specific markers both (that SP-B) bronchiolar CC10) lineages. express Bmi1, supports self-renewal stem cells. Lung adenomas spontaneously develop in aging Runx3+/- mice ( approximately 18 months birth) invariably reduced levels Runx3. As very rare these adenomas, provide an animal model tumorigenesis recapitulates preneoplastic stage human adenocarcinoma development, independent K-Ras mutation. We conclude cell downregulation causally linked to