In:
Development, The Company of Biologists, Vol. 134, No. 15 ( 2007-08-01), p. 2719-2725
Abstract:
β-catenin signaling is heavily involved in organogenesis. Here, we investigated how pancreas differentiation, growth and homeostasis are affected following inactivation of an endogenous inhibitor of β-catenin,adenomatous polyposis coli (Apc). In adult mice, Apc-deficient pancreata were enlarged, solely as a result of hyperplasia of acinar cells, which accumulatedβ-catenin, with the sparing of islets. Expression of a target ofβ-catenin, the proto-oncogene c-myc (Myc), was increased in acinar cells lacking Apc, suggesting that c-mycexpression is essential for hyperplasia. In support of this hypothesis, we found that conditional inactivation of c-myc in pancreata lacking Apc completely reversed the acinar hyperplasia. Apc loss in organs such as the liver, colon and kidney, as well as experimental misexpression of c-myc in pancreatic acinar cells, led to tumor formation with high penetrance. Surprisingly, pancreas tumors failed to develop following conditional pancreas Apc inactivation. In Apc-deficient acini of aged mice,our studies revealed a cessation of their exaggerated proliferation and a reduced expression of c-myc, in spite of the persistent accumulation of β-catenin. In conclusion, our work shows that β-catenin modulation of c-myc is an essential regulator of acinar growth control, and unveils an unprecedented example of Apc requirement in the pancreas that is both temporally restricted and cell-specific. This provides new insights into the mechanisms of tumor pathogenesis and tumor suppression in the pancreas.
Type of Medium:
Online Resource
ISSN:
1477-9129
,
0950-1991
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2007
detail.hit.zdb_id:
2007916-3
SSG:
12
Permalink