title: Entopic overexpression of Ascl2 does not accelerate tumourigenesis in ApcMin mice.
abstract: OBJECTIVE
  Expression of the Wnt target gene ASCL2 is elevated in 78% of intestinal neoplasia datasets (Oncomine), suggesting a role for deregulated ASCL2 in the aetiology of intestinal tumourigenesis. Furthermore, ectopic expression of Ascl2 has previously been shown to lead to hyperplasia in the mouse. However, elevated levels of ASCL2 does not have an impact on the overall survival or recurrence-free survival rates in colorectal cancer patients. Here the authors use a novel mouse model to analyse the role of Ascl2 in intestinal tumourigenesis and address the controversy surrounding the relevance of this gene to the aetiology of colorectal cancer.
  
  
  METHODS
  The authors have generated a mouse possessing a transgene carrying the Ascl2 gene together with its endogenous promoter and regulatory regions, thereby elevating Ascl2 expression in an authentic manner. The authors have further intercrossed these Ascl2 overexpressers to the classic Apc(Min)   model, to study the consequence of elevated Ascl2 expression in intestinal tumourigenesis.
  
  
  RESULTS
  Here the authors genetically demonstrate that elevated expression of Ascl2 in a Wnt signalling dependent manner specifically in the stem cell compartment of the intestine neither increases tumour formation nor diminishes survival in a well established intestinal tumour model, the Apc(min)   mouse.
  
  
  CONCLUSIONS
  The authors conclude that ectopic expression of Ascl2 is more important in the aetiology of neoplasia than overexpression of Ascl2.
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK. reedkr@cf.ac.uk
authors.forename: Karen R
authors.initials: KR
authors.lastname: Reed
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Tunster
authors.forename: Madeleine
authors.initials: M
authors.lastname: Young
authors.forename: Adam
authors.initials: A
authors.lastname: Carrico
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: John
authors.forename: Alan R
authors.initials: AR
authors.lastname: Clarke
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000401:mortality; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; C489311:Ascl2 protein, mouse