title: UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6.
abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.
authors.affiliation: Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501, Japan; Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Miyata
authors.affiliation: Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ichihara
authors.affiliation: Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Orie
authors.initials: O
authors.lastname: Tajima
authors.affiliation: Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Sobue
authors.affiliation: Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kambe
authors.affiliation: Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Sugiura
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan. Electronic address: koichi@med.nagoya-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501, Japan; Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology / Q000528:radiation effects*; D008544:Melanocytes / Q000201:enzymology* / Q000276:immunology / Q000528:radiation effects; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D012799:Sialyltransferases / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
keywords: Keratinocyte; Melanocyte; Melanoma; ST8SIA1; TNFα; UV-B