Abstract 79: Deletion of STAT3 in a mouse model for metastatic melanoma

Abstract

Abstract The incidence of metastatic melanoma, a very aggressive type of human skin cancer, has steadily increased over the last years and is associated with high mortality. Activating mutations in the N-Ras proto-oncogene are characteristic for cutaneous melanoma. The most frequent mutation found in N-Ras is a lysine substitution of glutamine at codon 61 (Q61K) constitutively activating the protein. Together with other mutations, especially inactivation of the CDKN2A locus, it is sufficient for spontaneous melanoma formation and subsequent metastasis formation in mice. STAT3 proteins are highly phosphorylated in melanoma. We identified strong STAT3 expression and activation in 70% of patients that show melanoma brain metastases. Here, we investigated whether deletion of this transcription factor in a mouse model expressing mutant N-RasQ61K transgene under the control of the tyrosinase promoter in combination with a homozygous CDKN2A deletion, leads to modified melanoma formation. Interestingly, we found decreased survival in male mice that do not express STAT3 in melanoma cells. We analyzed primary tumor development, metastasis, and survival using histo-pathological examination between groups of STAT3 positive and negative mice. To further assess whether the enhanced tumor progression upon loss of STAT3 is a cell autonomous effect we established melanoma cell lines derived from mouse tumors with or without STAT3. These novel cell lines will be used to analyze growth and survival properties. We will also test the influence of a functional immune system to question immunoediting by xenotransplantation experiments. Citation Format: Alexander Swoboda, Isabel J. Sobieszek, Michaela Schlederer, Safia Zahma, Jelena Marjanovic, Valeria Poli, Lukas Kenner, Markus Hengstschläger, Mario Mikula, Richard Moriggl. Deletion of STAT3 in a mouse model for metastatic melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 79. doi:10.1158/1538-7445.AM2014-79