Targeting RAS-MAPK-ERK and PI3K-AKT-mTOR signal transduction pathways to chemosensitize anaplastic thyroid carcinoma
2014
Аутори:
Milosevic, ZoricaPešić, Milica
Stankovic, Tijana
Dinić, Jelena
Milovanovic, Zorka
Stojsic, Jelena
Džodić, Radan R.
Tanić, Nikola
Banković, Jasna Z.
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
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.
Извор:
Translational Research, 2014, 164, 5, 411-423
DOI: 10.1016/j.trsl.2014.06.005
ISSN: 1878-1810