RGD Reference Report - Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas. - Rat Genome Database

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Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.

Authors: Strom, A  Bonal, C  Ashery-Padan, R  Hashimoto, N  Campos, ML  Trumpp, A  Noda, T  Kido, Y  Real, FX  Thorel, F  Herrera, PL 
Citation: Strom A, etal., Development. 2007 Aug;134(15):2719-25. Epub 2007 Jun 27.
RGD ID: 2317191
Pubmed: PMID:17596282   (View Abstract at PubMed)
DOI: DOI:10.1242/dev.02875   (Journal Full-text)

beta-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 beta-catenin, adenomatous polyposis coli (Apc). In adult mice, Apc-deficient pancreata were enlarged, solely as a result of hyperplasia of acinar cells, which accumulated beta-catenin, with the sparing of islets. Expression of a target of beta-catenin, the proto-oncogene c-myc (Myc), was increased in acinar cells lacking Apc, suggesting that c-myc expression 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 beta-catenin. In conclusion, our work shows that beta-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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hyperplasia  ISOApc (Mus musculus)2317191; 2317191 RGD 
Hyperplasia  IMP 2317191 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Apc  (APC regulator of WNT signaling pathway)

Genes (Mus musculus)
Apc  (APC, WNT signaling pathway regulator)

Genes (Homo sapiens)
APC  (APC regulator of WNT signaling pathway)


Additional Information