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Σάββατο 24 Νοεμβρίου 2018

Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo

Abstract

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf V600E ‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr Cre ERT 2/+ ; Braf LSL ‐V600E/+ ; Pten flox/flox ) to Sirt5 ‐/‐ knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5 ‐/‐ mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf V600E ‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.

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