1272 p21Waf1/Cip1 is differentially expressed in epidermal versus follicular melanocytes and melanoma cells and is phenotypically regulated by UVB-mediated apoptosis

Melanoma is a malignant cancer of pigment-producing cells in our skin, exhibiting an exceptional mutational burden and drug resistance. This is partly due to exposure to UV radiation and a higher incidence of genetic variations associated with fair skin, freckles, and red hair, which can lead to DNA damage and melanoma development. Defective apoptosis pathways constitute one barrier to melanoma treatment. Thus, targeting apoptosis regulators is a promising approach to sensitizing melanomas for treatment. Using a multiplex approach, we studied the expression of apoptosis markers in primary human epidermal and follicular melanocytes, (HEM, HFM), and compared it with selected melanoma cell lines of variable melanin levels and subtype (FM55P, FM55M, SK-MEL-23). A distinct apoptosis profile was found between normal melanocytes (HEM, HFM), primary (FM55P), and metastatic (FM55M, SK-MEL-23) melanoma cells. In particular, the cyclin-dependent kinase inhibitor p21 (p21WAF1/Cip1) was found to be much more highly expressed in normal melanocytes (HEM, HFM) than in melanoma cells. Western-blot analysis revealed the highest expression of p21 in bulb-derived melanocytes (HFM), followed by HEM and a much-reduced p21 expression in melanoma cell lines. This may relate to unique traits of melanocytes in hair follicle that naturally proliferate and apoptose during the hair growth cycle and are remarkably resistant to melanomagenesis. Ultraviolet radiation (UVB) induces melanocyte cell death in vitro and upon UVB exposure (300mJ/cm2) p21 protein expression increased in HEM and primary melanoma cells (FM55P), with linked to decreased expression of Bcl2. This suggests that disruption of cell cycle repair processes controlled by p21 in pigment cells may constitute a way for preventing melanoma progression.