A new mouse model of pancreatic cancer indicates that disruption of the transforming growth factor-β (TGFβ) signalling pathway leads to the development of premalignant lesions.

Pancreatic cancer has the worst prognosis of all gastrointestinal cancers, largely due to a lack of early clinical symptoms and effective treatments once the disease is diagnosed. So, good in vivo models of early pancreatic tumour development are needed to identify new diagnostic and treatment strategies.

Various genetic changes are known to contribute to the genesis of pancreatic cancer. In particular, >50% of human tumours have disrupted TGFβ signalling owing to the homozygous deletion of the signal transducer SMAD4. To investigate further, Chenzhong Kuang, Yan Chen and colleagues transgenically expressed rat SMAD7, an inhibitor of the TGFβ signalling pathway, specifically in the pancreatic tissue of mice.

Having verified that SMAD7 was expressed at detectable levels, the authors analysed the histological changes within the pancreas. At 6 months of age these mice developed pancreatic intraepithelial neoplasia (PanIN), a precursor of invasive disease. Immunohistochemical analyses verified that the tumours arose from the pancreatic ductal epithelium and showed that these cells were actively proliferating.

The authors conclude that disruption of TGFβ signalling, which is known to be antiproliferative early on in tumorigenesis, promotes PanIN development and suggest that their mouse model should prove useful for identifying new treatments for this aggressive disease.