| Literature DB >> 25016932 |
Zorica Milosevic1, Milica Pesic1, Tijana Stankovic1, Jelena Dinic1, Zorka Milovanovic2, Jelena Stojsic3, Radan Dzodic4, Nikola Tanic1, Jasna Bankovic5.
Abstract
Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive and chemoresistant tumor with dismal prognosis. Most ATCs harbor mutations that activate RAS/MAPK/ERK and PI3K/AKT/mTOR pathways. Therefore, we investigated and correlated the expression of phosphatase and tensin homolog, pERK, and pAKT proteins as well as mutations of BRAF, RAS, and p53 genes in samples of patients with ATC. Furthermore, we evaluated the potential of inhibition of these pathways on chemosensitization of ATC using 2 thyroid carcinoma cell lines (FRO and SW1736). Our results revealed a negative correlation between the activity of RAS-MAPK-ERK and PI3K-AKT-mTOR pathways in samples of patients. To be specific, the PI3K-AKT-mTOR pathway was suppressed in patients with activated NRAS or high pERK expression. In vitro results suggest that the inhibition of either RAS-MAPK-ERK or PI3K-AKT-mTOR components may confer sensitivity of thyroid cancer cells to classic chemotherapeutics. This may form a basis for the development of novel genetic-based therapeutic approach for this cancer type.Entities:
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Year: 2014 PMID： 25016932 DOI： 10.1016/j.trsl.2014.06.005
Source DB: PubMed Journal: Transl Res ISSN： 1878-1810 Impact factor: 7.012