Surprisingly, angiotensin II, which mediates structural changes in the heart and is a component of the local renin-angiotensin system in pancreatic cancer cells, also increases IGF-IIR expression via the activation of downstream kinases, which leads to sirtuin 1 (SIRT1) degradation via the proteasomes and prevents it from deacetylating heat shock transcription factor 1 (HSF1). Here, REN is linked to familial pancreatic carcinoma.