Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10895548 | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 2015 | 13 Pages |
Abstract
Inactivation of tumor suppressor genes (TSG) in normal cells provides a viability/growth advantage that contributes cell-autonomously to cancer. More than a decade ago claims arose that the RUNX3 member of the RUNX transcription factor family is a major TSG inactivated in gastric cancer, a postulate extended later to other cancers. However, evidence that Runx3 is not expressed in normal gastric and other epithelia has challenged the RUNX3-TSG paradigm. Here we critically re-appraise this paradigm in light of recent high-throughput, quantitative genome-wide studies on thousands of human samples of various tumors and new investigations of the role of Runx3 in mouse cancer models. Collectively, these studies unequivocally demonstrate that RUNX3 is not a bona fide cell-autonomous TSG. Accordingly, RUNX3 is not recognized as a TSG and is not included among the 2000 cancer genes listed in the “Cancer Gene Census” or “Network for Cancer Genes” repositories. In contrast, RUNX3 does play important functions in immunity and inflammation and may thereby indirectly influence epithelial tumor development.
Keywords
IBDmethylation specific polymerase chain reactionN-methyl-N-nitrosoureaCGHMSPMNUDMBAqRT-PCRGITtPAHSCDRGnatural killerRNA in situ hybridizationloss of heterozygosityImmunohistochemistryIHCCrohn's diseaseInflammatory bowel diseasecomparative genomic hybridizationGastrointestinal tractGastric cancerHematopoietic stem cellDendritic cellTranscription factorLOHFishGenome-wide association studyGWASfluorescent in-situ hybridizationQuantitative reverse transcriptase polymerase chain reactionAntibodySNPFetal liverdorsal root ganglia
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Cancer Research
Authors
Joseph Lotem, Ditsa Levanon, Varda Negreanu, Omri Bauer, Shay Hantisteanu, Joseph Dicken, Yoram Groner,