Molecular and Cellular Endocrinology

These data,including,ros level,insulin secretion,the expression of genes associated with glycolysis, was exhibited.

Raw data of western blot and fluorescent probe are included, other data such as HE and Masson (TIF), we originally prepared to upload, but we do not know why it keeps showing errors, we feel sorry for that.

The data show the roles of LAT1 in growth hormone (GH)-producing pituitary tumor cells, GH4 cells. Briefly, GH4 cells express higher LAT1 gene levels compared to rat normal pituitary tissues (Fig. 1A). A selective LAT1 inhibitor, JPH203, does not change LATs expression profiles in GH4 cells (Fig.1B and C), and pharmacological LAT1 inhibition by JPH203 suppresses leucine uptake and cell growth in GH4 cells (Fig. 2A and C, and Supplemental Fig. 1). Deprivation of leucine reduces cell growth in GH4 cells (Fig 2B). JPH203 suppresses GH production and secretion in GH4 cells (Fig. 3A, B, and C). JPH203 also reduces prolactin gene expression levels. Genetic downregulation of LAT1 shows similar effects on cell growth and hormone production (Fig. 4A, B, and C, and Supplemental Fig 3). JPH203 does not alter the activity of the mTOR pathway (Fig. 5A, B, and C). Pharmacological mTOR inhibition by rapamycin suppresses cell growth but does not alter GH production in GH4 cells (Fig. 6A, B, and C). JPH203 does not induce apoptosis in GH4 cells (Fig. 7). A combination of JPH203 and rapamycin shows additive anti-tumor effects on cell growth in GH4 cells (Supplemental Fig. 4) .

Reagent and Ressources, DNA Deposited data Sofwares

This record contains data related to article: "A novel insight into the anticancer mechanism of metformin in pancreatic neuroendocrine tumor cells." The antidiabetic drug metformin displays anticancer properties in several neoplasms. In pituitary NETs, aryl hydrocarbon receptor-interacting protein (AIP) is up-regulated by the somatostatin analog octreotide. Metformin inhibited QGP-1 cell proliferation in a dose- and time-dependent manner, at concentrations similar to those achievable in treated patients (−31 ± 12%, p < 0.05 vs basal at 100 μM). Moreover, metformin decreased pancreatic neuroendocrine tumors (PAN-NETs) cell proliferation (−62 ± 15%, p < 0.0001 vs basal at 10 mM), without any additive effect when combined with octreotide. Both octreotide and metformin induced AIP up-regulation. AIP silencing abolished the reduction of mTOR phosphorylation induced by metformin and octreotide. Moreover, metformin decreased HSP70, increased Zac1 and AhR expression; these effects were abolished in AIP silenced QGP-1 cells. In conclusion, metformin acts as an anticancer agent in PAN-NET cells, its activity is mediated by AIP and its interacting proteins. These findings provide a novel insight into the antitumorigenic mechanism of metformin.