Fig. 2: Aberrant activation of Cdk5 generates PanNETs in an inducible bi-transgenic mouse model.

A Schematic of genetic system for regulated tissue-specific expression of p25-GFP. B Immunoblot for expression of p25GFP in islets isolated from transgene negative (−) and INS-p25OE (+) mice with (on) or without (off) administration of 1 g/L Dox for 4–5 weeks. C H&E stain and immunofluorescence of sections of pancreas from INS-p25OE mice at 4 weeks post-p25-GFP induction. D Representative gross image of a pancreatic mass from INS-p25OE mice. E Immunoblot for expression of p25-GFP in pancreatic mass, liver, and kidney at 12 months induction. H&E stain (F), and immunostains (G) of primary PanNET from an INS-25OE animal. Scale bars = 100 μm. H Axial MRI sections from a representative INS-p25OE mouse. PanNET circumscribed in yellow. I Quantitation of tumor volume over time from a representative INS-p25OE mouse. J Tumor growth, normalized to initial volume, during the linear growth phase; males (M; n = 4) and females (F; n = 3 for each group) administered dox since weaning (on) or dox since weaning followed by discontinuation for 5 weeks after initial tumor detection (off). On and off dox only compared within female groups. K Immunoblot for expression of SSTR2 and actin in INS-p25OE tumors.