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The Runx3 Controversy Rages On

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A team of researchers led by Kyoto University's Yoshiaki Ito published a paper in Cell in 2002, saying that the gene Runx3 is expressed in gastrointestinal tract epithelium, and acts to suppress the development of gastric tumors, says Science's Dennis Normile. A year earlier, a group led by Yoram Groner at the Weizmann Institute of Science in Israel published a paper in Mechanisms of Development on Runx3, and had concluded that the gene is not expressed in gastrointestinal tract epithelium. Now, Normile reports, Groner's group is formally challenging the results that Ito — now at the National University of Singapore — published almost 10 years ago, calling his results "irreproducible." Groner's group filed a formal complaint with NUS, which has launched an investigation. If Groner's challenge is successful, Normile adds, "hundreds of scientific papers might be affected."

In a paper published in EMBO Molecular Medicine in August, Groner's group said it used several different measures to rule out both the possibility that Runx3 is expressed in the gastrointestinal epithelium and that it acts as a tumor suppressor. In addition, the group says, none of the subsequent 286 papers based at least in part on Ito's work went back and re-examined the assertion that Runx3 is expressed in this tissue, Normile reports. For his part, Ito says his group has been unable to replicate part of the original experiment, but he adds that as the mouse line he used has been bred continuously for 10 years, it's possible that the marker gene he inserted has been silenced. "In a long rebuttal submitted to EMBO Molecular Medicine ... Ito points to other studies supporting his group's work, particularly their own 2005 paper in Cancer Research finding Runx3 in the human gastrointestinal tract, a finding he says has been replicated by at least one other group," Normile writes.

Many cancer researchers say they are dismayed by the controversy. It's also unclear what could happen to those 286 papers should Ito's conclusions be successfully challenged, Normile adds.

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