Disruption of mutated BRAF signaling modulates thyroid cancer phenotypeReportar como inadecuado

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BMC Research Notes

, 7:187



BackgroundThyroid cancer is the most common endocrine-related cancer in the United States and its incidence is rising rapidly. Since among various genetic lesions identified in thyroid cancer, the BRAFV600E mutation is found in 50% of papillary thyroid cancers and 25% of anaplastic thyroid cancers, this mutation provides an opportunity for targeted drug therapy. Our laboratory evaluated cellular phenotypic effects in response to treatment with PLX4032, a BRAFV600E-specific inhibitor, in normal BRAF-wild-type thyroid cells and in BRAFV600E-positive papillary thyroid cancer cells.

MethodsNormal BRAF-wild-type thyroid cells and BRAFV600E-mutated papillary thyroid cancer cells were subjected to proliferation assays and analyzed for cell death by immunofluorescence. Cell cycle status was determined using an EdU uptake assay followed by laser scanning cytometry. In addition, expression of proteins within the MAPK signal transduction pathway was analyzed by Western blot.

ResultsPLX4032 has potent anti-proliferative effects selectively in BRAF-mutated thyroid cancer cells. These effects appear to be mediated by the drug’s activity of inhibiting phosphorylation of signaling molecules downstream of BRAF within the pro-survival MAPK pathway. Interestingly, PLX4032 promotes the phosphorylation of these signaling molecules in BRAF-wild-type thyroid cells.

ConclusionsThese findings support further evaluation of combinational therapy that includes BRAFV600E inhibitors in thyroid cancer patients harboring the BRAFV600E mutation.

KeywordsThyroid cancer BRAFV600E mutation PLX4032 MAPK signal transduction pathway Targeted therapy Kinase inhibitors Electronic supplementary materialThe online version of this article doi:10.1186-1756-0500-7-187 contains supplementary material, which is available to authorized users.

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Autor: Elyse K Hanly - Shilpi Rajoria - Zbigniew Darzynkiewicz - Hong Zhao - Robert Suriano - Neha Tuli - Andrea L George - Robe

Fuente: https://link.springer.com/

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