Inhibiting BRAF Oncogene-Mediated Radioresistance Effectively Radiosensitizes BRAF^V600E-Mutant Thyroid Cancer Cells by Constraining DNA Double-Strand Break Repair.

ABSTRACT:

Purpose

Activating BRAF mutations, most commonly BRAF^V600E, are a major oncogenic driver of many cancers. We explored whether BRAF^V600E promotes radiation resistance and whether selectively targeting BRAF^V600E with a BRAF inhibitor (vemurafenib, BRAFi) sensitizes BRAF^V600E thyroid cancer cells to radiotherapy.

Experimental design

Immunoblotting, neutral comet, immunocytochemistry, functional reporter, and clonogenic assays were used to analyze the outcome and molecular characteristics following radiotherapy with or without BRAF^V600E or vemurafenib in thyroid cancer cells.

Results

BRAF^V600E thyroid cancer cell lines were associated with resistance to ionizing radiation (IR), and expression of BRAF^V6

SUBMITTER: Robb R 

PROVIDER: S-EPMC6677585 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature