title: Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.forename: Yael
authors.initials: Y
authors.lastname: Bernstein
authors.forename: Varda
authors.initials: V
authors.lastname: Negreanu
authors.forename: Karen Rae
authors.initials: KR
authors.lastname: Bone
authors.forename: Amir
authors.initials: A
authors.lastname: Pozner
authors.forename: Raya
authors.initials: R
authors.lastname: Eilam
authors.forename: Joseph
authors.initials: J
authors.lastname: Lotem
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D050677:Core Binding Factor Alpha 3 Subunit / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D011506:Proteins / Q000378:metabolism; D022661:RNA, Untranslated; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D022661:RNA, Untranslated; D011993:Recombinant Fusion Proteins; C493726:Runx1 protein, mouse; C493730:Runx3 protein, mouse; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase