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High expression of Mcl‐1L via the MEK ‐ ERK ‐phospho‐ STAT 3 (Ser727) pathway protects melanocytes and melanoma from UVB ‐induced apoptosis
Author(s) -
Fukumoto Takeshi,
Iwasaki Tetsushi,
Okada Taro,
Hashimoto Takanori,
Moon Youbin,
Sakaguchi Masanobu,
Fukami Yasuo,
Nishigori Chikako,
Oka Masahiro
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12330
Subject(s) - apoptosis , mapk/erk pathway , uvb induced apoptosis , melanoma , stat3 , cancer research , chemistry , phosphorylation , cell culture , biology , microbiology and biotechnology , programmed cell death , caspase , biochemistry , genetics
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 ‐ STAT 3 ( STAT 3 phosphorylated at Ser727) pathway. The Ser727 phosphorylation facilitated nuclear localization of STAT 3. In melanoma cells, the expression levels of Mcl‐1L varied depending on the cell line. WM 39 melanoma cells expressed high levels of Mcl‐1L via the MEK ‐ ERK ‐ pS ‐ STAT 3 pathway and were resistant to UVB ‐induced apoptosis without up‐regulation of Mcl‐1L. In melanocytes and in WM 39 cells, transfection with Mcl‐1 si RNA 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 ‐ STAT 3 pathway protects melanocytes and melanoma cells from UVB ‐induced apoptosis.

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