Expression of IGF/mTOR Pathway Components in Human Pheochromocytomas and In Vitro Inhibition of PC12 Rat Pheochromocytoma Cell Growth by mTOR Inhibitors

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Introduction: The pathogenesis of pheochromocytomas (pheo) is poorly understood and malignant pheo need new treatment options. mTOR inhibitors, as sirolimus(S) and everolimus(E), are promising antineoplastic drugs.

Aim(s): To evaluate whether the IGF/mTOR pathways have a role in the pathogenesis and whether S and E may have antiproliferative effects in pheo.

Materials and methods: In 24 human pheo and two normal adrenal medulla (NM), we evaluated the mRNA expression of: IGFI, IGFII, IGF-I-Receptor [IGF-R], Insulin-Receptor[IR]A, IRB, IGF-IIR, IGF-Binding-Proteins [BP] 1, 2, 3 and 6, mTOR, 4EBP1 and p70S6K (by qPCR). We tested the dose- and time-dependent effects of S and E on cell growth in the PC12 rat pheo cell line.

Conference: 8th Annual ENETSConcerence (2011)

Presenting Author:

Authors: De Martino M, Feelders R, van Koetsveld P, De Krijger R, Sprij-Mooij D,

Keywords: IGF, mTOR, everolimus, sirolimus, pheochromocytomas, PC12, adrenal, neuroendocrine, tumor,