¹Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, UK

²Section of Biomedical Sciences, Medical School, Teviot Place, Edinburgh EH8 9AG, UK

³Department of Biomedical Sciences, Cardiff University, Cardiff CF10 3US, UK

⁴Brain Tumor Research Center, Montreal Neurological Institute, McGill University, 3801 rue Université, Montreal, Qc, Canada, H3A 2B4

Correspondence to: M L Hooper, E-mail: m.hooper@ed.ac.uk

Mutations in the tumour suppressor genes SMAD4 (DPC4, deleted in pancreatic cancer locus 4) and adenomatous polyposis coli (APC) have been implicated in the development of pancreatic cancer in humans. Treatment of wild-type, Smad4^+/-, Apc^Min/+ or Apc^Min/+Smad4^+/- mice with N-Nitroso-N-Methyl Urea (NMU) results in abnormal foci in pancreatic acinar cells characterized by increased levels of -catenin. Previously such foci have been shown to be the precursors of pancreatic neoplasia. Interestingly, only NMU-treated Apc^Min/+Smad4^+/- mice exhibit a significant increase in abnormal pancreas, which was found to be due to increased number of abnormal foci rather than increased focus size. A range of foci sizes were analysed, but only smaller abnormal foci were characterized by morphological nuclear atypia. These studies suggest functional co-operation between TGF- and Wnt signalling pathways in the suppression of pancreatic tumorigenesis in the mouse.

Oncogene (2002) 21, 4696-4701. doi:10.1038/sj.onc.1205673

pancreas; SMAD4; APC; mouse