Inhibition of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors

Surgery
Mark S CohenJ F Moley

Abstract

Most medullary thyroid carcinomas (MTCs) result from gain-of-function mutations in the RET proto-oncogene, which encodes a transmembrane tyrosine kinase receptor. Systemic therapies have not been effective in treating this disease. We evaluated the effects of 3 tyrosine kinase inhibitors (TKIs) on MTC cell growth and RET tyrosine kinase activity by using an in vitro model. An MTC cell line (TT cells, RETc634 mutant) cultured in RPMI medium was exposed to varying concentrations of STI571, genistein, or allyl-geldanamycin with controls (no TKI) for 3 to 48 hours. Cellular protein was analyzed by immunoprecipitated Western blot analysis probing with a monoclonal antiphosphotyrosine antibody. Cell proliferation was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2'-deoxyuridine (BrdU) assays. RET phosphorylation was inhibited at 24 hours of exposure to 5 to 20 micromol/L STI571 and 48 hours of exposure to genistein (200 micromol/L) and allyl-geldanamycin (6 micromol/L). RET protein was detected in equal concentrations in all experimental conditions. MTT and BrdU assays demonstrated a dose-dependent decrease in TT cell proliferation with exposure to the 3 TKIs. These TKIs selectively inhi...Continue Reading

References

Oct 1, 1988·The Journal of Clinical Endocrinology and Metabolism·N A SamaanR C Hickey
Aug 1, 1980·The Journal of Clinical Endocrinology and Metabolism·M R StjernholmL J Deftos
Aug 1, 1996·Thyroid : Official Journal of the American Thyroid Association·J BrierleyT Panzarella
Dec 1, 1996·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·K M FifeC L Harmer
Jun 1, 1997·Annals of Surgery·J F MoleyM K DeBenedetti
Mar 28, 1998·Blood Cells, Molecules & Diseases·C Gambacorti-PasseriniN B Lydon
Jul 29, 1998·Journal of Internal Medicine·J F MoleyS A Wells
Jun 24, 2000·World Journal of Surgery·S A Wells, C Franz
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Apr 6, 2001·International Journal of Cancer. Journal International Du Cancer·A GrecoM A Pierotti

❮ Previous
Next ❯

Citations

Oct 13, 2006·Pituitary·Yoshiki MurakumoMasahide Takahashi
Aug 29, 2003·Current Treatment Options in Oncology·Jeffrey F Moley
Jun 22, 2005·Current Treatment Options in Oncology·Amber Traugott, Jeffrey F Moley
May 31, 2007·Journal of Biosciences·Len Neckers
Mar 12, 2004·Cancer Letters·Masatoshi IchiharaMasahide Takahashi
Oct 5, 2006·Nature Clinical Practice. Oncology·Matthias Drosten, Brigitte M Pützer
Jun 3, 2005·Thyroid : Official Journal of the American Thyroid Association·H M van SantenT Vulsma
Dec 21, 2004·Journal of Internal Medicine·A MachensH Dralle
Apr 8, 2010·The Journal of Clinical Endocrinology and Metabolism·Bruce G RobinsonRobert Haddad
Jul 28, 2007·European Journal of Endocrinology·Karin Frank-RaueFriedhelm Raue
Sep 23, 2014·Critical Reviews in Oncology/hematology·V MarottaA Faggiano
Oct 20, 2015·Journal of Pediatric Hematology/oncology·Vidya K NarayananMohamad G Shaikh
May 17, 2013·Expert Opinion on Pharmacotherapy·Vincenzo MarottaAntongiulio Faggiano
Dec 5, 2013·Expert Opinion on Drug Discovery·Michael W Sim, Mark Steven Cohen
Dec 21, 2010·Seminars in Oncology·Susan C Pitt, Jeffrey F Moley
Oct 20, 2009·The Surgical Clinics of North America·Tricia A Moo-YoungJeffrey F Moley
Mar 19, 2008·Current Problems in Surgery·Elizabeth G GrubbsDouglas B Evans
Apr 1, 2008·Surgical Oncology Clinics of North America·Matthew L White, Gerard M Doherty
Feb 20, 2008·Molecular and Cellular Endocrinology·S DvorakovaB Bendlova
Aug 4, 2007·Endocrinology and Metabolism Clinics of North America·Catherine Dinauer, Gary L Francis
Aug 4, 2007·Endocrinology and Metabolism Clinics of North America·Douglas W Ball
Jun 9, 2007·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·I M OskamM W M van den Brekel
May 20, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Bibi TahiraMahmood Rasool
Feb 19, 2005·Journal of Surgical Oncology·Frank J Quayle, Jeffrey F Moley
Nov 30, 2006·Journal of Surgical Oncology·Elizabeth A Fialkowski, Jeffrey F Moley
May 6, 2011·Head & Neck·Cesar A PerezEzra E W Cohen
Jan 20, 2005·Surgery·Ganesh R PantaLawrence T Kim
Jul 10, 2004·Trends in Molecular Medicine·Brigitte M Pützer, Matthias Drosten
Jun 29, 2005·Cytokine & Growth Factor Reviews·Elena ArighiHannu Sariola
May 26, 2004·Clinics in Laboratory Medicine·Nicole Massoll, Ernest L Mazzaferri
Mar 30, 2007·Annales d'endocrinologie·D VezzosiP Caron
Oct 3, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Qinyi ZhouJiadong Wang
Apr 25, 2008·Molecular Genetics and Metabolism·Catherine E Lewis, Michael W Yeh
Sep 21, 2016·Expert Opinion on Therapeutic Patents·Luca MologniLeonardo Scapozza
Sep 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Muralidhar BeeramEric K Rowinsky
Jan 20, 2018·Endocrine-related Cancer·Sara RedaelliLuca Mologni
Nov 25, 2003·Expert Review of Molecular Diagnostics·Maria João BugalhoLuís Sobrinho
May 8, 2018·Cellular & Molecular Biology Letters·Jing LiuChunyan Zheng
Mar 29, 2011·Critical Reviews in Toxicology·Susanne AndresAlfonso Lampen
Feb 14, 2006·Molecular Endocrinology·Aaron CranstonItalia Bongarzone
Jun 21, 2007·The Journal of Clinical Endocrinology and Metabolism·J W B de GrootE E Voest

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.