Abstract
The selective increase of Na(+)/I(-) symporter (NIS)-mediated active iodide uptake in thyroid cells allows the use of radioiodine I(131) for diagnosis and targeted treatment of thyroid cancers. However, NIS-mediated radioiodine accumulation is often reduced in thyroid cancers due to decreased NIS expression/function. As PI3K signaling is overactivated in many thyroid tumors, we investigated the effects of inhibitors for PI3K, Akt, or mTORC1 as well as their interplay on NIS modulation in thyroid cells under chronic TSH stimulation. PI3K inhibition by LY294002 increased NIS-mediated radioiodide uptake (RAIU) mainly through upregulation of NIS expression, however, mTORC1 inhibition by Rapamycin did not increase NIS-mediated RAIU despite increased NIS protein levels. In comparison, Akt inhibition by Akti-1/2 did not increase NIS protein levels, yet markedly increased NIS-mediated RAIU by decreasing iodide efflux rate and increasing iodide transport rate and iodide affinity of NIS. The effects of Akti-1/2 on NIS-mediated RAIU are not detected in nonthyroid cells, implying that Akti-1/2 or its derivatives may represent potential pharmacological reagents to selectively increase thyroidal radioiodine accumulation and therapeutic effic...Continue Reading
References
Feb 1, 1979·Journal of Immunogenetics·A M Heumann, C Stiffel
Nov 14, 1998·The Journal of Clinical Endocrinology and Metabolism·B CaillouJ M Bidart
Mar 7, 2000·Oncogene·L A Cass, J L Meinkoth
Aug 22, 2000·Oncogene·O M TsygankovaJ L Meinkoth
Mar 10, 2001·Molecular and Cellular Biology·O M TsygankovaJ L Meinkoth
Apr 6, 2001·The Journal of Biological Chemistry·C RiedelN Carrasco
Apr 21, 2001·Oncogene·I CiulloE V Avvedimento
Oct 20, 2001·Molecular Pharmacology·L IacovelliA De Blasi
Nov 10, 2001·The Journal of Clinical Endocrinology and Metabolism·M R CastroJ C Morris
Jan 31, 2002·Molecular Endocrinology·Bibian García, Pilar Santisteban
Jun 29, 2002·The Journal of Biological Chemistry·Liguang LouDaniel L Altschuler
Nov 1, 2002·Pediatric Research·Aneeta PatelGary L Francis
Jul 11, 2003·Oncogene·Jeffrey A KnaufJames A Fagin
Aug 11, 2004·The Journal of Biological Chemistry·Derek K MarseeSissy M Jhiang
Sep 27, 2006·Oncogene·X WanL J Helman
Jul 20, 2007·Endocrine-related Cancer·Douangsone D VadysirisackSissy M Jhiang
Aug 24, 2007·The Journal of Biological Chemistry·Il-Ha LeeDavid I Cook
Oct 5, 2007·The Journal of Biological Chemistry·Douangsone D VadysirisackSissy M Jhiang
Jan 19, 2008·Molecular Endocrinology·Miguel A ZaballosPilar Santisteban
Mar 6, 2008·The Journal of Clinical Endocrinology and Metabolism·Takahiko KogaiGregory A Brent
Aug 30, 2008·The Journal of Clinical Investigation·Arkaitz CarracedoPier Paolo Pandolfi
Sep 3, 2008·The Journal of Endocrinology·Takahiko KogaiGregory A Brent
Feb 24, 2009·Current Opinion in Cell Biology·Jeffrey A Knauf, James A Fagin
Apr 9, 2009·Cancer Research·Emi OhashiGregory A Brent
Jul 14, 2009·PloS One·Peng HouMingzhao Xing
Mar 17, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Tadashi YoshidaPatrice Delafontaine
Apr 16, 2010·The Journal of Endocrinology·Elaine Cristina Lima de SouzaDenise Pires de Carvalho
Jun 29, 2010·Thyroid : Official Journal of the American Thyroid Association·Mingzhao Xing
Citations
Dec 20, 2013·Journal of Molecular Endocrinology·Maria D'AgostinoDiego Russo
Jan 10, 2014·Thyroid : Official Journal of the American Thyroid Association·Aparna LakshmananSissy M Jhiang
Sep 23, 2014·Hormones & Cancer·Aparna LakshmananSissy M Jhiang
Feb 14, 2016·Molecular and Cellular Endocrinology·Caroline Serrano-NascimentoMaria Tereza Nunes
Aug 27, 2015·Endocrine-related Cancer·Maria Isabel C Vieira CordioliJanete M Cerutti
Jun 6, 2014·The Lancet. Diabetes & Endocrinology·Christine SpitzwegJohn C Morris
Nov 19, 2014·Endocrine-related Cancer·Aparna LakshmananSissy M Jhiang
Mar 20, 2015·PloS One·Hui YangYu Duan
Jun 28, 2016·Journal of Experimental & Clinical Cancer Research : CR·Chen-Tian ShenQuan-Yong Luo
Jun 8, 2017·Acta Cirúrgica Brasileira·Peng JiaBin Liu
Jan 16, 2014·Endocrinology·Caroline Serrano-NascimentoMaria Tereza Nunes
Jul 25, 2014·Nucleic Acids Research·Hideaki KumeKumiko Ui-Tei
Feb 19, 2014·Journal of Cellular and Molecular Medicine·Leni MoldovanMelissa Piper
Sep 28, 2014·Nucleic Acids Research·Cornelia VeselyMichael F Jantsch
Jan 14, 2020·Thyroid : Official Journal of the American Thyroid Association·Ji Min OhByeong-Cheol Ahn
Nov 20, 2012·Molecular Endocrinology·Miguel A Zaballos, Pilar Santisteban
Feb 3, 2016·The Biochemical Journal·Elisabeth DarrouzetThierry Pourcher
Sep 24, 2015·Oncotarget·Aparna LakshmananSissy M Jhiang
Jul 17, 2019·Thyroid : Official Journal of the American Thyroid Association·Rebecca J ThompsonChristopher J McCabe
Oct 1, 2019·Endocrinology and Metabolism·Jierui LiuJun Liang
Sep 16, 2018·Cancer Research·Fang FengCharis Eng
Jan 28, 2021·International Journal of Molecular Sciences·Yoon Ju ChoiYong Hyun Jeon
Nov 23, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Oussama ElMokhRoch-Philippe Charles
Jun 9, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·X CaiN Li
Jul 30, 2021·Food & Function·Li ZhangJiandong Bao
Oct 16, 2021·Frontiers in Oncology·Fang FengHui Wang