Protective effect of hyperpigmented skin on UV-mediated cutaneous cancer development
Protective effect of hyperpigmented skin on UV-mediated cutaneous cancer development
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DOI：
10.1038/sj.jid.5700659
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发表时间：
2007-05-01
影响因子：
6.5
通讯作者：
Nakashima, Izumi
中科院分区：
文献类型：
--
作者：
Kato, Masashi;Ohgami, Nobutaka;Nakashima, Izumi
最近，我们将242系的原始有毛RET转基因小鼠与无毛小鼠杂交，并建立了无毛RET-（HL/RET）转基因小鼠系（242-hr/hr），其具有色素沉着的皮肤但没有肿瘤。在这项研究中，我们研究了HL/RET转基因小鼠的色素沉着皮肤对紫外线照射介导的皮肤癌发展的影响。尽管存在黑色素瘤诱导的转基因RET癌基因，但对该小鼠系的紫外线照射从未诱导黑色素瘤。相反，色素沉着的皮肤有效地保护了皮肤中UV介导的鳞状细胞癌的发展。可能在这一结果的基础上，色素沉着过度保护皮肤免受损伤，并阻断伴随的信号转导，用于多种细胞蛋白的酪氨酸磷酸化和细胞外信号调节的c-Jun N-末端和p38激酶的活化/磷酸化。因此，我们证明了色素沉着介导的体内保护对紫外线照射诱导的皮肤癌。
Recently, we crossed an original haired RET-transgenic mouse of line 242 with a hairless mouse and established a hairless RET-(HL/RET)-transgenic mouse line (242-hr/hr) with hyperpigmented skin but no tumors. In this study, we examined the effect of hyperpigmented skin in HL/RET-transgenic mice on UV irradiation-mediated cutaneous cancer development. UV irradiation to this mouse line never induced melanoma despite the presence of melanoma-inducible transgenic RET oncogenes. On the contrary, the hyperpigmented skin efficiently protected UV-mediated squamous carcinoma development in the skin. Probably underlying this result, hyperpigmentation protected the skin from damage and blocked the accompanying signal transduction for tyrosine phosphorylation of multiple cellular proteins and activation/phosphorylation of extracellular signal-regulated, c-Jun N-terminal, and p38 kinases. Thus, we demonstrated hyperpigmentation-mediated in vivo protection against UV irradiation-induced skin cancer.