Fig 2: SSTR2 reintroduction does not sensitize human neuroendocrine tumor (NET) cells to octreotide treatment. (A) Human SSTR2-transfected NET cell lines BON and QGP-1 were treated with increasing concentrations of octreotide (0.1 pM–10 µM), incubated for 96 h and analyzed for viability (metabolic activity). (B) For comparison, wild-type and ratSSTR2-GFP-transfected RIN-1038 cells were analyzed in the same way. Data represent mean ± SEM (n = 2–4).

Fig 3: 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.

Fig 4: Basal levels of SSTR2 protein expression. (A) Basal expression level of SSTR2 in human fibroblast cell lines (917 and WI38), aggressive thyroid cancer cell lines (TPC, FTC236, and Hth7) and in neuroendocrine cancer cell lines (medullary thyroid cancer: TT and MZ; pancreatic NE cancer: BON; pulmonary carcinoid: H727). H727 cell line has the lowest basal expression of SSTR2 among all NET cells (Supplementary Figure S1). (B) A comparison of basal SSTR2 expression at the protein level between two pulmonary carcinoid cell lines: UMC-11 and H727 (Supplementary Figure S2). Error bars show standard deviation.

Fig 5: Increase in SSTR2 protein expression. (A) Upregulation of SSTR2 expression in NET cell lines by HDAC inhibitor treatment. The pulmonary carcinoid cell line, H727, showed the highest fold induction of SSTR2 (Supplementary Figure S3). (B) Ratio of SSTR2 protein expression relative to GADPH protein expression in NET cell lines after incubation with HDAC inhibitors (C) Upregulation of SSTR2 expression in the cell surface proteins of pulmonary carcinoid cell line H727 after TDP-A and VPA administration (Supplementary Figure S4).