Sunitinib inhibits MEK/ERK and SAPK/JNK pathways and increases sodium/iodide symporter expression in papillary thyroid cancer

Thyroid : Official Journal of the American Thyroid Association
Mike S FentonJerome M Hershman

Abstract

Sunitinib malate (Sutent, Pfizer, Inc.; SU11248) is a selective, multitargeted inhibitor of receptor tyrosine kinases and has been shown to inhibit receptors for VEGF, PDGF, KIT, FLT3, and RET. The objective of this study was to determine the effects of sunitinib on signal transduction pathways and on gene expression of iodide-metabolizing proteins in papillary cancer cells with the RET/PTC1 rearrangement. We investigated the effects of sunitinib on cell growth, signal transduction pathways, and thyroid-specific gene expression in papillary thyroid cancer (PTC) cell lines that had the RET/PTC1 rearrangement. Sunitinib inhibited proliferation of RET/PTC1 subclones in a time- and dose-related manner. The mean 50% lethal concentration in the RET/PTC1 subclones was 1.81 microM. Incubation of RET/PTC1 cells with 1 microM sunitinib inhibited their migration potential and transformed their morphology. Sunitinib inhibited RET autophosphorylation at Y1062 and the activation of signal transducer and activator of transcription 3 by blocking Y705 phosphorylation. Sunitinib caused cell cycle arrest in the G0/G1 phase and dephosphorylation of retinoblastoma protein, but did not induce apoptosis. Western blot analysis of the p38, MEK/ERK, and...Continue Reading

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Citations

Dec 24, 2011·Thyroid : Official Journal of the American Thyroid Association·Maria D'AgostinoDiego Russo
Feb 19, 2011·Current Opinion in Oncology·Yassine Lalami, Ahmad Awada
Jul 1, 2014·World Journal of Gastroenterology : WJG·Anne ElsnerRobert Jaster
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Mar 24, 2012·The Journal of Clinical Endocrinology and Metabolism·Annamaria PiscazziMatteo Landriscina
Oct 11, 2017·Current Medicinal Chemistry·Silvia Martina FerrariPoupak Fallahi
Sep 27, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Guanglei GaoWenyan Ma
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Sep 28, 2021·Frontiers in Cell and Developmental Biology·Albert Manzano-MuñozJoan Montero

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flow cytometry
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