Metastasising Melanoma

Here, we study the role of STAT3 in a metastasizing malignant melanoma model driven by oncogenic RAS. Mice develop lung, lymph node and liver metastases. We generated new melanoma compound mouse models that harbors a floxed STAT3 allele and a Cre transgene specifically expressed under the tyrosinase promoter, which is only active in melanocytes of the skin. These mice were crossed to mice lacking the Ink4a gene locus, which is known to lead to a predisposition to melanoma in patients. Additionally, the model harbors a typical early occurring melanoma mutation, the N-RasQ61K mutation, also expressed under the tyrosinase promoter. The N-RasQ61K mutation leads to hyperpigmentation of the skin, as can be seen e.g. in human nevi. We successfully isolated oncogenic RAS-driven and Ink4a-deficient melanoma cell lines from mice harboring a deletion of the Stat3 gene and from control mice that still express STAT3. We found that STAT3 signaling in malignant melanoma is essential for pigmentation and protection from UV irradiation.

Analysis of human melanoma cell lines:
Immunofluorescence for the transcription factors C/EBPα and MITF expression in murine melanoma cells, regulated by the JAK/STAT pathway control melanoma growth and survival. The experiment was performed in collaboration with Mario Mikula from the Medical University Vienna.
Analysis of human melanoma cell lines

To top