title: High expression of Mcl-1L via the MEK-ERK-phospho-STAT3 (Ser727) pathway protects melanocytes and melanoma from UVB-induced apoptosis.
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 UVB-induced apoptosis.
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukumoto
authors.affiliation: Research Center for Environmental Genomics, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.|Department of Biology, Kobe University Graduate School of Science, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: Division of Biochemistry, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Biology, Kobe University Graduate School of Science, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Biology, Kobe University Graduate School of Science, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.
authors.forename: Youbin
authors.initials: Y
authors.lastname: Moon
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Research Center for Environmental Genomics, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.|Department of Biology, Kobe University Graduate School of Science, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Fukami
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oka
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015854:Up-Regulation
chemical_list: C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D050796:STAT3 Transcription Factor