Telomere dysfunction in Tert knockout mice delays Braf^V600E -induced melanoma development.

ABSTRACT: Telomerase activation is a crucial step in melanomagenesis, often occurring because of ultraviolet radiation (UVR)-induced mutations at the telomerase gene (TERT) promoter and rendering TERT transcription in response to the activated Raf-MAP kinase pathway by BRAF^V600E mutation. Due to the excessively long telomeres in mice, this process does not occur during melanomagenesis in mouse models. To investigate the impact of telomere dysfunction on melanomagenesis, Braf^V600E was induced in generations 1 and 4 (G1 and G4) of Tert^-/- mice. Our findings revealed that, regardless of UVR exposure, melanoma development was delayed in G4 mice, which had shorter telomeres compared to G1 and wild-type C57BL/6J (G0) mice. Moreover, many G4 tumors displayed an accumulation

SUBMITTER: Zhang J 

PROVIDER: S-EPMC10840707 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature