Distinct genetic alterations in the mitogen-activated protein kinase pathway dictate sensitivity of thyroid cancer cells to mitogen-activated protein kinase kinase 1/2 inhibition.

ABSTRACT:

Background

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway plays an important role in papillary and anaplastic thyroid cancer (PTC and ATC) due to activating mutations in BRAF, RAS, or rearrangements in RET/PTC1. The objective of this study was to thoroughly test whether the BRAF V600E mutation predicts response to mitogen-activated protein kinase kinase 1/2 (MKK1/2) inhibition, as shown in other tumor types, using an authenticated panel of thyroid cancer cell lines.

Methods

PTC and ATC cells harboring distinct mutations in the MAPK pathway were treated with two different inhibitors selective for MKK1/2 (CI-1040 or U0126). The consequences of MKK1/2 inhibition on cell growth, survival, invasion, and MAPK signaling was determine

SUBMITTER: Schweppe RE 

PROVIDER: S-EPMC2857444 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature