Loss of Phd2 cooperates with BRAF^V600E to drive melanomagenesis.

ABSTRACT: Prolyl hydroxylase domain protein 2 (PHD2) is a well-known master oxygen sensor. However, the role of PHD2 in tumor initiation remains controversial. We find that during the transition of human nevi to melanoma, the expression of PHD2 protein is significantly decreased and lower expression PHD2 in melanoma is associated with worse clinical outcome. Knockdown of PHD2 leads to elevated Akt phosphorylation in human melanocytes. Mice with conditional melanocyte-specific expression of Phd2^lox/lox (Tyr::CreER;Phd2^lox/lox) fail to develop pigmented lesions. However, deletion of Phd2 in combination with expression of BRaf^V600E in melanocytes (Tyr::CreER;Phd2^lox/lox;BRaf^CA) leads to the development of melanoma with 100% penetrance and frequent

SUBMITTER: Liu S 

PROVIDER: S-EPMC6303344 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature