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Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function
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Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function
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Journal Article
Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function
2011
Overview
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.
Publisher
Nature Publishing Group UK,WILEY‐VCH Verlag,EMBO Press,WILEY-VCH Verlag
Subject
/ beta-Galactosidase - metabolism
/ Cancer
/ Core Binding Factor Alpha 2 Subunit - metabolism
/ Core Binding Factor Alpha 3 Subunit - deficiency
/ Core Binding Factor Alpha 3 Subunit - genetics
/ Core Binding Factor Alpha 3 Subunit - metabolism
/ Epithelial Cells - metabolism
/ Green Fluorescent Proteins - metabolism
/ Mice
/ Recombinant Fusion Proteins - metabolism
/ Reverse Transcriptase Polymerase Chain Reaction
/ Software
/ Tumor Suppressor Proteins - deficiency
/ Tumor Suppressor Proteins - genetics
/ Tumor Suppressor Proteins - metabolism
/ Tumors
