Article

Stabilization of β-catenin impacts pancreas growth

Department of Medicine, University of California, San Francisco, San Francisco, California, United States
Development (Impact Factor: 6.27). 06/2006; 133(10):2023-32. DOI: 10.1242/dev.02366
Source: PubMed

ABSTRACT A recent study has shown that deletion of beta-catenin within the pancreatic epithelium results in a loss of pancreas mass. Here, we show that ectopic stabilization of beta-catenin within mouse pancreatic epithelium can have divergent effects on both organ formation and growth. Robust stabilization of beta-catenin during early organogenesis drives changes in hedgehog and Fgf10 signaling and induces a loss of Pdx1 expression in early pancreatic progenitor cells. Together, these perturbations in early pancreatic specification culminate in a severe reduction of pancreas mass and postnatal lethality. By contrast, inducing the stabilized form of beta-catenin at a later time point in pancreas development causes enhanced proliferation that results in a dramatic increase in pancreas organ size. Taken together, these data suggest a previously unappreciated temporal/spatial role for beta-catenin signaling in the regulation of pancreas organ growth.

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    • "In the adult pancreas, Wnt signalling is inactive (Pasca di Magliano et al, 2007), yet it is essential for its development during embryogenesis (Murtaugh et al, 2005; Heiser et al, 2006). The embryonic pancreas harbours multipotent progenitor cells that can give rise to all pancreatic lineages (acinar, duct and endocrine) (Zaret and Grompe, 2008). "
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    • "Thus, in our next round of experiments, we will explore in more detail the molecular mechanisms by which PAUF signaling can stabilize and activate β-catenin. Our observation that β-catenin stabilization can enhance the proliferation of pancreatic cell lines is strongly supported by other studies showing that activation of β-catenin alone is sufficient to induce pancreatic tumorigenesis using Cre/lox transgenic mice (Heiser et al., 2008), and also that deletion of the β-catenin gene results in a loss of pancreas mass during development (Heiser et al., 2006). We suggest that the rapid proliferation of pancreatic cancer cell lines can be explained at least in part by the elevated cyclin D1 and c-Jun expression caused by PAUF-induced β-catenin. "
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