Antiproliferative effects of Src inhibition on medullary thyroid cancer

The Journal of Clinical Endocrinology and Metabolism
Zijuan LiuFiemu Nwariaku

Abstract

There is no effective treatment for recurrent or metastatic medullary thyroid cancer (MTC). Hereditary MTC is associated with mutations in the RET protooncogene, which encodes for a tyrosine kinase. We postulated that Src tyrosine kinases regulate MTC proliferation. Proliferation of the human MTC cell line, TT, was examined in the presence of a Src-specific tyrosine kinase inhibitor, PP2, or genistein. Cell counts were performed with a Coulter counter or by flow cytometry. DNA synthesis was evaluated by bromodeoxyuridine incorporation. A cell death ELISA was used to assess apoptosis. Akt phosphorylation was determined by Western immunoblot. MAPK activity was measured using an immunoprecipitation kinase assay, and MAPK inhibition was achieved with SB202190 (p38 MAPK) and PD098059 (MAPK kinase). Data were analyzed by ANOVA. Compared with controls, PP2 reduced DNA synthesis, abolished Akt phosphorylation, and increased apoptosis. The MAPK kinase inhibitor, PD098059, attenuated DNA synthesis, whereas genistein caused modest declines in cell count and DNA synthesis and minimal changes in apoptosis. We conclude that Src-dependent MTC proliferation occurs via increased DNA synthesis and reduced apoptosis. The latter effect may be medi...Continue Reading

Citations

Oct 20, 2006·Apoptosis : an International Journal on Programmed Cell Death·Lin Ping-YuanShih Wen-Ling
May 22, 2008·Breast Cancer Research and Treatment·S HiscoxR I Nicholson
Jul 21, 2005·Thyroid : Official Journal of the American Thyroid Association·Herbert ChenJamie J Van Gompel
Jun 29, 2010·Thyroid : Official Journal of the American Thyroid Association·Tirtha Das, Ross Cagan
Jan 24, 2006·Anti-cancer Drugs·Ting ChenChristopher C Taylor
May 17, 2011·Future Oncology·Lucia Brilli, Furio Pacini
Dec 14, 2007·Journal of Endocrinological Investigation·R MorisiD Russo
Dec 21, 2010·Seminars in Oncology·Susan C Pitt, Jeffrey F Moley
Mar 19, 2008·Current Problems in Surgery·Elizabeth G GrubbsDouglas B Evans
Mar 18, 2005·Cancer Science·Yoshinori KodamaMasahide Takahashi
Nov 26, 2008·Biochemical Pharmacology·Cinzia LanziFranco Zunino
Sep 13, 2005·Surgery·Ganesh R PantaLawrence T Kim
Mar 30, 2007·Annales d'endocrinologie·D VezzosiP Caron
Jun 13, 2017·International Journal of Molecular Sciences·Carlos F L GonçalvesAndrea C F Ferreira
Jan 4, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Adriano SpreaficoAnnalisa Santucci
Sep 7, 2017·Cell Reports·Tirtha Kamal Das, Ross Leigh Cagan
Jun 1, 2020·Fitoterapia·Javad Sharifi-RadRaffaele Pezzani

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis