High expression of Mcl-1L via the MEK-ERK-phospho-STAT3 (Ser727) pathway protects melanocytes and melanoma from UVB-induced apoptosis

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
Takeshi FukumotoMasahiro Oka

Abstract

Ultraviolet (UV) B is a major factor in melanomagenesis. This fact is linked to the resistance of melanocytes to UVB-induced apoptosis. In this study, we characterized the involvement of Mcl-1L in the regulation of UVB-induced apoptosis in melanocytes and in melanoma cells. In melanocytes, apoptosis was not evident at 24 h after UVB irradiation. The Mcl-1L expression increased after UVB irradiation, and the high Mcl-1L expression continued for at least 24 h. This UVB-dependent increase in Mcl-1L was mediated by the MEK-ERK-pS-STAT3 (STAT3 phosphorylated at Ser727) pathway. The Ser727 phosphorylation facilitated nuclear localization of STAT3. In melanoma cells, the expression levels of Mcl-1L varied depending on the cell line. WM39 melanoma cells expressed high levels of Mcl-1L via the MEK-ERK-pS-STAT3 pathway and were resistant to UVB-induced apoptosis without up-regulation of Mcl-1L. In melanocytes and in WM39 cells, transfection with Mcl-1 siRNA promoted UVB-induced apoptosis. Immunohistochemical studies showed that melanoma cells in in situ lesions expressed high amounts of Mcl-1L. These results indicate that the high expression of Mcl-1L mediated by the MEK-ERK-pS-STAT3 pathway protects melanocytes and melanoma cells from U...Continue Reading

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