Development

Blood and Guts

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Science  03 May 2002:
Vol. 296, Issue 5569, pp. 809
DOI: 10.1126/science.296.5569.809b

The Runt domain transcription factors are downstream targets of transforming growth factor-β (TGF-β), implicated in regulating mammalian developmental processes, including hematopoiesis (RUNX1) and osteogenesis (RUNX2). Li et al. report that the third runt-related factor, RUNX3, is a negative cell growth regulator. RUNX3 is expressed primarily in the mouse gastrointestinal tract, particularly in stomach epithelial cells. Mice lacking RUNX3 exhibited increased proliferation and decreased apoptosis of gastric epithelial cells. Primary cultures of RUNX3-null gastric epithelial cells were less sensitive to the growth inhibitory effects of TGF-β as compared to wild-type cells. In gastric cancer cell lines and tumor-derived tissue, RUNX3 is frequently silenced and undetectable. Thus RUNX3 is anti-oncogenic and its loss may account for certain cases of gastric cancer.

Loss of functional RUNX1 is related to leukemogenesis in mice, and its mutations are associated with acute myeloid leukemia. Kalev-Zylinska et al. have cloned and characterized RUNX1 in zebrafish and show that it is also involved in hematopoeisis. Reducing its expression resulted in defective blood and vasculature development. This genetically tractable model system may prove useful to screen for molecules that modulate RUNX protein function.—LDC

Cell109, 113 (2002); Development129, 2015 (2002).

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