ECE2011 Poster Presentations Adrenal medulla (7 abstracts)
Expression of IGF/mTOR pathway components in human pheochromocytomas and in vitro inhibition of PC12 rat pheochromocytoma cell growth by mTOR inhibitors
M C De Martino 1, , R A Feelders 1 , P M van Koetsveld 1 , R R De Krijger 3 , J A M J L Janssen 1 , D Sprij-Mooij 1 , S W J Lamberts 1 , W W de Herder 1 , Annamaria Colao 2 , Rosario Pivonello 2 & Leo Hofland 1
1Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands; 2Department of Endocrinology, Federico II University, Naples, Italy; 3Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
The pathogenesis of pheochromocytomas (pheo) is poorly understood and malignant pheo need new treatment options. mTOR inhibitors, as sirolimus (S) and everolimus (E), are new promising antineoplastic drugs.
Aim: To evaluate whether the IGF/mTOR pathways have a role in the pathogenesis and whether S and E may have antiproliferative effects in pheo.
In 24 human pheo and two normal adrenal medulla (NM), we evaluated 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). We tested the dose- and time-dependent effects of S and E on cell growth in the PC12 rat pheo cell line.
In pheo, we observed a high expression of IGFII mRNA and an increased IRA/IRB ratio. The IGFI-R mRNA levels and the IRA/IRB ratio were higher in pheo than in NM. The mRNA levels of mTOR, IGFIIR, BP1 and 6 were lower in pheo than in NM. S and E were able to suppress PC12 growth in a dose and time-dependent manner, but S was more potent than E.
The results of the current study suggest a role of the IGF system in the pathogenesis of pheo. mTOR inhibitors can inhibit the in vitro cell proliferation of rat pheo cells, suggesting that mTOR inhibitors and/or other compounds targeting the IGF system may have a role in the treatment of malignant pheo.
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Endocrine Abstracts
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