Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia

Brenner, Ori; Levanon, Ditsa; Negreanu, Varda; Golubkov, Olga; Fainaru, Ofer; Woolf, Eilon; Groner, Yoram

doi:10.1073/pnas.0407180101

Cited by 159 publications

(162 citation statements)

References 67 publications

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“…Although we confirmed that this antibody recognizes Runx3 in the gastric epithelial cells, the signal was weaker than that obtained by R3-1E10 and R3-3F12 (Figures 3c and d). As expected from results by Brenner et al (2004), G-poly reacted poorly with the wild-type gastric epithelium. Thus, R3-10C7 and G-poly, both recognizing the same region of RUNX3 (Figures 2c and d), show weak specificity for Runx3 in gastric epithelial cells.…”

Section: Runx3 Expression In Gastrointestinal Tract Epithelium K Ito supporting

confidence: 87%

“…This analysis revealed that the Runx3 mRNA is expressed by GIT epithelial cells at about 10% of the levels in blood cells (data not shown). As for the other Runx genes, Runx1 is clearly expressed by GIT epithelium as observed by others (Levanon et al, 2001;Brenner et al, 2004). Very low levels of Runx2 expression were detected (data not shown).…”

supporting

confidence: 76%

“…Several other groups have also demonstrated the expression of RUNX3 mRNA and/or protein in gastric epithelial cells (Osaki et al, 2004;Oshimo et al, 2004;Torquati et al, 2004;Wei et al, 2005;Zavros et al, 2005;Katuri et al, 2006;Peng et al, 2006;Usui et al, 2006). However, others have failed to demonstrate the expression of Runx3 in normal gastric epithelial cells immunohistochemically using G-poly and this has led them to question its contribution to carcinogenesis in GIT epithelium (Levanon et al, 2001(Levanon et al, , 2003Brenner et al, 2004, Carvalho et al, 2005. Here, we resolve the controversy by identifying the unusual properties of the anti-RUNX3 antibodies used for these studies and we report the production of a series of monoclonal antibodies that can clearly identify Runx3 in epithelial cells of the GIT (Yano et al, 2006;Ito et al, 2008).…”

mentioning

confidence: 99%

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Runx3 expression in gastrointestinal tract epithelium: resolving the controversy

Ito

Inoue

et al. 2009

Oncogene

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We reported earlier that RUNX3 is expressed in human and mouse gastrointestinal tract (GIT) epithelium and that it functions as a tumor suppressor in gastric and colorectal tissues. However, there have been conflicting reports describing the absence of Runx3 in GIT epithelial cells. A part of the controversy may be derived from the use of a specific antibody by other groups (referred to as G-poly). Here, we show further evidence to support our earlier observations and provide a possible explanation for this apparent controversy. We generated multiple anti-RUNX3 monoclonal antibodies and found that RUNX3 antibodies recognizing the RUNX3 N-terminal region (residues 1-234) react with RUNX3 in gastric epithelial cells, whereas those recognizing the C-terminal region (beyond residue 234) did not. G-poly primarily recognizes the region beyond 234 and hence, is unable to detect Runx3 in this tissue.

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Section: Runx3 Expression In Gastrointestinal Tract Epithelium K Ito supporting

confidence: 87%

supporting

confidence: 76%

mentioning

confidence: 99%

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Runx3 expression in gastrointestinal tract epithelium: resolving the controversy

Ito

Inoue

et al. 2009

Oncogene

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“…It should be noted, however, that Groner and coworkers reported conflicting data: they could not detect Runx3 in the mouse gastrointestinal tract (GIT) epithelium (Brenner et al, 2004). We have earlier found that RUNX3 mRNA transcripts in GIT are relatively low compared with peripheral blood .…”

Section: Controversy On Runx3 Expression In Gastrointestinal Tract Epmentioning

confidence: 95%

“…For example, overexpression of a pro-inflammatory cytokine interleukin 1b in the gastric epithelium was sufficient to induce inflammation and hyperplasia (Tu et al, 2008). Consistent with this notion, Groner's group attributed the GIT hyperplasia exhibited by their Runx3 knockout mice to inflammatory bowel disease caused by Runx3 deficiency in leukocytes in the GIT (Brenner et al, 2004;Levanon and Groner, 2009), as they could not detect Runx3 expression in the GIT epithelium of wildtype mice. In contrast, however, the knockout mice generated by Ito et al (2008) exhibited minimal inflammation and as such was unlikely to cause hyperplasia in the GIT epithelium.…”

Section: Controversy On Runx3 Expression In Gastrointestinal Tract Epmentioning

confidence: 96%

RUNX3 is multifunctional in carcinogenesis of multiple solid tumors

2010

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The study of RUNX3 in tumor pathogenesis is a rapidly expanding area of cancer research. Functional inactivation of RUNX3-through mutation, epigenetic silencing, or cytoplasmic mislocalization-is frequently observed in solid tumors of diverse origins. This alone indicates that RUNX3 inactivation is a major risk factor in tumorigenesis and that it occurs early during progression to malignancy. Conversely, RUNX3 has also been described to have an oncogenic function in a subset of tumors. Although the mechanism of how RUNX3 switches from tumor suppressive to oncogenic activity is unclear, this is of clinical relevance with implications for cancer detection and prognosis. Recent developments have significantly contributed to our understanding of the pleiotropic tumor suppressive properties of RUNX3 that regulate major signaling pathways. This review summarizes the important findings that link RUNX3 to tumor suppression.

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Runx2: A master organizer of gene transcription in developing and maturing osteoblasts

Schroeder

Jensen

Westendorf

2005

Birth Defects Research Pt C

283

235

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Runx2 is essential for osteoblast development and proper bone formation. A member of the Runt domain family of transcription factors, Runx2 binds specific DNA sequences to regulate transcription of numerous genes and thereby control osteoblast development from mesenchymal stem cells and maturation into osteocytes. Although necessary for gene transcription and osteoblast development, Runx2 is not sufficient for optimal gene expression or bone formation. Runx2 cooperates with numerous proteins, including transcription factors and cofactors, is posttranslationally modified, and associates with the nuclear matrix to integrate a variety of signals and organize crucial events during osteoblast development and maturation. Consistent with its role as a master organizer, alterations in Runx2 expression levels are associated with skeletal diseases. Runx2 haploinsufficiency causes cleidocranial dysplasia, while Runx2 overexpression is common in many bone‐metastatic cancers. In this review, we summarize the molecular mechanisms by which Runx2 integrates signals through coregulatory interactions, and discuss how its role as a master organizer may shift depending on promoter structure, developmental cues, and cellular context. Birth Defects Research (Part C) 75:213–225, 2005. © 2005 Wiley‐Liss, Inc.

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Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia

Cited by 159 publications

References 67 publications

Runx3 expression in gastrointestinal tract epithelium: resolving the controversy

Runx3 expression in gastrointestinal tract epithelium: resolving the controversy

RUNX3 is multifunctional in carcinogenesis of multiple solid tumors

Runx2: A master organizer of gene transcription in developing and maturing osteoblasts

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