2023 article
Telomere dysfunction in Tert knockout mice delays Braf<SUP>V600E</SUP>-induced melanoma development
Zhang, J., Zhang, F., Porter, K. I., Dakup, P. P., Wang, S., Robertson, G. P., … Zhu, J. (2023, September 20). INTERNATIONAL JOURNAL OF CANCER.
author keywords: BRAF; melanoma; mouse model; telomerase; telomere dysfunction
TL;DR:
It is suggested that telomere dysfunction hampers melanomagenesis, and targeting telomeres crisis‐mediated genomic instability may hold promise for the prevention and treatment of melanoma.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: October 23, 2023
AbstractTelomerase 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 BRAFV600E 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, BrafV600E 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 of excessive DNA damage, as evidenced by increased γH2A.X staining. Tumors from UVR‐exposed mice exhibited elevated p53 protein expression. Cultured tumor cells isolated from G4 mice displayed abundant chromosomal fusions and rearrangements, indicative of telomere dysfunction in these cells. Additionally, tumor cells derived from UVB‐exposed mice exhibited constitutively elevated expression of mutant p53 proteins, suggesting that p53 was a target of UVB‐induced mutagenesis. Taken together, our findings suggest that telomere dysfunction hampers melanomagenesis, and targeting telomere crisis‐mediated genomic instability may hold promise for the prevention and treatment of melanoma.