Ablation of epidermal RXRα in cooperation with activated CDK4 and oncogenic NRAS generates spontaneous and acute neonatal UVB induced malignant metastatic melanomas.

ABSTRACT:

Background

Understanding the underlying molecular mechanisms involved in the formation of cutaneous malignant melanoma is critical for improved diagnosis and treatment. Keratinocytic nuclear receptor Retinoid X Receptor α (RXRα) has a protective role against melanomagenesis and is involved in the regulation of keratinocyte and melanocyte homeostasis subsequent acute ultraviolet (UV) irradiation.

Methods

We generated a trigenic mouse model system (RXRα ^ep-/- | Tyr-NRAS ^Q61K | CDK4 ^R24C/R24C ) harboring an epidermal knockout of Retinoid X Receptor α (RXRα ^ep-/- ), combined with oncogenic NRAS ^Q61K (constitutively active RAS) and activated CDK4 ^R24C/R24C (constitutively active CDK4). Those mice were subjected to

SUBMITTER: Chagani S 

PROVIDER: S-EPMC5679438 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature