Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 project, Oral Science Research Center, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, Seoul, Republic of Korea.
Differentiation. 2011 Apr;81(4):261-8. doi: 10.1016/j.diff.2011.02.001. Epub 2011 Mar 1.
The runt-domain transcription factor Runx3 plays crucial roles during development such as regulating gene expression. It has been shown that Runx3 is involved in neurogenesis, thymopoiesis and functions like a tumor suppressor. Runx3 null mouse die soon after birth as a result of multiple organ defects. Runx3 null mouse lung shows an abnormal phenotype and loss of Runx3 induced remodeling in the lung. Interestingly, lung adenocarcinoma is observed in Runx3 heterozygous mice at 18 months of age. During lung development various cellular and molecular events occur such as cell proliferation, cell death, differentiation and epithelial-mesenchymal transition (EMT). To understand the specific lethal events in Runx3 null mice, we examined cellular and molecular networks involved in EMT, and EMT inducers were quantified by RT-qPCR during lung development. Excessive EMT was observed in lungs at PN1 day in Runx3 null mice and PN18 months in Runx3 heterozygous mice. Pharmacologic inhibition of EMT was used to curb tumor progression. In this study, U0126 was injected to pregnant mouse for inhibition of pERK signaling. After U0126 treatment, life spans of newborn mice were increased and lung hyperplasia was partially rescued by down-regulated cell proliferation and EMT. Our data suggest that Runx3 is involved in crucial regulation of alveolar differentiation and tumor suppression in developing mouse lung.
runt 结构域转录因子 Runx3 在发育过程中发挥着重要作用，如调节基因表达。已经表明，Runx3 参与神经发生、胸腺生成，并具有肿瘤抑制因子的功能。Runx3 缺失的小鼠在出生后不久就因多个器官缺陷而死亡。Runx3 缺失的小鼠肺显示出异常表型和肺中 Runx3 诱导的重塑缺失。有趣的是，Runx3 杂合子小鼠在 18 个月时观察到肺腺癌。在肺发育过程中，会发生各种细胞和分子事件，如细胞增殖、细胞死亡、分化和上皮-间充质转化（EMT）。为了了解 Runx3 缺失小鼠中特定的致死事件，我们检查了 EMT 相关的细胞和分子网络，并通过 RT-qPCR 在肺发育过程中量化了 EMT 诱导物。在 Runx3 缺失小鼠的 PN1 天和 Runx3 杂合子小鼠的 PN18 个月的肺中观察到 EMT 过度发生。我们使用 EMT 的药理学抑制来抑制肿瘤进展。在这项研究中，向怀孕的小鼠注射 U0126 以抑制 pERK 信号。在 U0126 处理后，新生小鼠的寿命延长，细胞增殖和 EMT 下调部分挽救了肺增生。我们的数据表明，Runx3 参与了发育中小鼠肺中肺泡分化和肿瘤抑制的关键调节。
