Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
EMBO Mol Med. 2011 Oct;3(10):593-604. doi: 10.1002/emmm.201100168. Epub 2011 Aug 8.
The Runx3 transcription factor regulates cell fate decisions during embryonic development and in adults. It was previously reported that Runx3 is strongly expressed in embryonic and adult gastrointestinal tract (GIT) epithelium (Ep) and that its loss causes gastric cancer. More than 280 publications have based their research on these findings and concluded that Runx3 is indeed a tumour suppressor (TS). In stark contrast, using various measures, we found that Runx3 expression is undetectable in GIT Ep. Employing a variety of biochemical and genetic techniques, including analysis of Runx3-GFP and R26LacZ/Runx3(Cre) or R26tdTomato/Runx3(Cre) reporter strains, we readily detected Runx3 in GIT-embedded leukocytes, dorsal root ganglia, skeletal elements and hair follicles. However, none of these approaches revealed detectable Runx3 levels in GIT Ep. Moreover, our analysis of the original Runx3(LacZ/LacZ) mice used in the previously reported study failed to reproduce the GIT expression of Runx3. The lack of evidence for Runx3 expression in normal GIT Ep creates a serious challenge to the published data and undermines the notion that Runx3 is a TS involved in cancer pathogenesis.
Runx3 转录因子在胚胎发育和成人过程中调节细胞命运决定。先前有报道称，Runx3 在胚胎和成人胃肠道（GIT）上皮（Ep）中强烈表达，其缺失会导致胃癌。超过 280 篇出版物基于这些发现进行了研究，并得出结论认为 Runx3 确实是一种肿瘤抑制因子（TS）。相比之下，我们使用各种方法发现，Runx3 在 GIT Ep 中无法检测到。通过使用各种生化和遗传技术，包括 Runx3-GFP 和 R26LacZ/Runx3(Cre) 或 R26tdTomato/Runx3(Cre) 报告菌株的分析，我们很容易在 GIT 嵌入的白细胞、背根神经节、骨骼元素和毛囊中检测到 Runx3。然而，这些方法都没有在 GIT Ep 中检测到可检测的 Runx3 水平。此外，我们对之前报道研究中使用的原始 Runx3(LacZ/LacZ) 小鼠的分析未能重现 Runx3 在 GIT 中的表达。正常 GIT Ep 中缺乏 Runx3 表达的证据，这对已发表的数据构成了严重挑战，并破坏了 Runx3 是参与癌症发病机制的 TS 的观点。
