Expression of IGF/mTOR Pathway Components in Human Pheochromocytomas and In Vitro Inhibition of PC12 rat Pheochromocytoma Cell Growth by mTOR Inhibitors alone and in Combination with the Dual IGFI-R/INS-R Antagonist OSI-906

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Introduction: Dysregulation of the mTOR and IGF pathways have been suggested to be involved in the pathogenesis of pheochromocytomas (PCC). mTOR inhibitors, such as sirolimus (S) and everolimus (E), as well as IGFI-R antagonists such as OSI-906, could be new a treatment for malignant PPC.

Aim(s): To evaluate expression of IGF/mTOR pathway components in PCC and to investigate whether IGF/mTOR pathway blockade has antiproliferative effects on PCC cells.

Materials and methods: The mRNA expression of: IGFI, IGFII, IGFI-Receptor [IGF-R], Insulin-Receptor[IR]A, IRB, IGFIIR, IGF-Binding-Proteins [BP] 1, 2, 3 and 6, mTOR, 4EBP1 and p70S6K (qPCR) was evaluated in 24 human PCC. The dose- and time-dependent effect of S, E and OSI-906 and the effect of combined selected doses of S and OSI-906 on cell growth and apoptosis in the PC12 rat PCC cell line was tested.

Conference: 11th Annual ENETSConcerence (2014)

Presenting Author: De Martino M

Authors: De Martino M, Feelders R, Dogan F, Van Koetsveld P, De Krijger R,

Keywords: IGF, mTOR, everolimus, OSI-906, pheochromocytoma, PC12, adrenal, neuroendocrine, tumor,