Prohibitin Is Overexpressed in Papillary Thyroid Carcinomas Bearing the BRAF V600E Mutation

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Abstract
Background: Prohibitin (PHB) is a multifunctional protein that is localized in different intracellular sites. PHB may exert different roles in tumorigenesis, having either a permissive action on tumor growth or an oncosuppressor role, depending on the cellular context. The objective of this study was to evaluate PHB expression in normal thyroid tissues, thyroid follicular adenomas (FAs), and papillary thyroid carcinomas (PTCs). Methods: PHB expression was analyzed by immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction (RT-PCR). Transfections in the BCPAP and TPC-1 thyroid cancer cell lines were used to evaluate the PHB promoter activity. Results: In terms of protein and mRNA levels, normal tissues from patients with serum thyrotropin (TSH) values >0.8 mU/L had PHB levels that were significantly reduced compared to specimens from patients with serum TSH values V600E mutation. Notably, cell transfection experiments suggested that presence of the BRAFV600E mutation may be associated to increase of the PHB promoter activity. Conclusions: PHB is overexpressed in PTCs bearing the BRAFV600E mutation. We postulate that the presence of the BRAFV600E mutation increases PHB promoter activity and therefore potentially mediates effects of this mutation on the behavior of BRAFV600E positive PTCs.

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