Poster presentation, P167

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Role of myc in melanoma

Malignant melanoma is one of the most highly invasive and metastatic tumors. Over the past years significant advances in understanding the cancer biology of melanoma have been achieved, but the molecular mechanisms involved in its development are still incompletely established. c-myc is an oncogenic transcription factor that is frequently upregulated in human malignancies including melanoma. We recently addressed the role of c-myc in the melanocyte differentiation during normal development. Mice conditionally deleted for c-myc in pigmented cells (Tyr::Cre, c-myc flox/flox) display a hair graying phenotype due to a reduction in melanocyte/melanoblast number during embryonic development. Interestingly, c-myc inactivation does not affect melanocytes differentiation and/or function. We therefore decided to address the role of c-myc in melanoma formation and maintenance. We made use of lentiviral constructs to block c-myc expression in the B16F1 established melanoma cell line and in primary melanoma cells isolated from Tyr::NrasQ61K mice. In both cases, shRNA-mediated inhibition of c-myc resulted in growth arrest and induction of differentiation. We then crossed conditional c-myc knockouts (Tyr::Cre, c-myc flox/flox) with mice spontaneously developing melanoma (Tyr::NrasQ61K, p16-/-). Preliminary analysis revealed proper melanoblast migration and/or survival but severe hair-graying and impaired melanocyte differentiation in Tyr::N-RasQ61K, p16-/-, Tyr::Cre, cMycflox/flox mice. We are currently monitoring these animals for spontaneous melanoma formation. Moreover, we plan to evaluate the effect of c-myc deletion on melanoma formation in the context of chemically-induced carcinogenesis. Finally, we want to generate an inducible c-myc conditional knockout melanoma mouse (Tyr::N-RasQ61K, p16-/-, Tyr::CreERT2, cMycflox/flox) to study the in-vivo role of c-myc in melanoma maintenance and survival.

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