Journal
GENES TO CELLS
Volume 21, Issue 2, Pages 185-199Publisher
WILEY
DOI: 10.1111/gtc.12330
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [26461692, 24791155]
- Hyogo Science and Technology Association
- Grants-in-Aid for Scientific Research [15K19689, 24791155, 26461692, 15K07930] Funding Source: KAKEN
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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 24h after UVB irradiation. The Mcl-1L expression increased after UVB irradiation, and the high Mcl-1L expression continued for at least 24h. 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 insitu 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 UVB-induced apoptosis.
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