Walker Graeme J, Kimlin Michael G, Hacker Elke, Ravishankar Sugandha, Muller H Konrad, Beermann Friedrich, Hayward Nicholas K
Oncogenomic Laboratory, Queensland Institute of Medical Research, Herston, Queensland, Australia.
J Invest Dermatol. 2009 Jan;129(1):184-93. doi: 10.1038/jid.2008.210. Epub 2008 Jul 17.
Melanocytes respond to UVR not only by producing melanin, but also by proliferating. This is essentially a protective response. We have studied the melanocyte proliferative response after a single UVR exposure to neonatal mice. At 3 days post-UVR in wild-type neonates we observed a marked melanocyte activation not seen in adults. Melanocytes migrated to the epidermal basal layer, their numbers peaking at 3-5 days after UVR then diminishing. They appeared to emanate from the hair follicle, migrating to the epidermis via the outer root sheath. In melanoma-prone mice with melanocyte-specific overexpression of Hras(G12V), basal layer melanocytes were increased in size and dendricity compared to UVR-treated wild-type mice. Melanocytes in mice carrying a pRb pathway cell-cycle defect (oncogenic Cdk4(R24C)) did not show an enhanced response to UVR such as those carrying Hras(G12V). The exquisite sensitivity to UVR-induced proliferation and migration that characterizes neonatal mouse melanocytes may partly explain the utility of this form of exposure for inducing melanoma in mice that carry oncogenic mutations.
黑素细胞对紫外线辐射（UVR）的反应不仅包括产生黑色素，还包括增殖。这本质上是一种保护反应。我们研究了新生小鼠单次暴露于UVR后的黑素细胞增殖反应。在野生型新生小鼠中，UVR照射后3天，我们观察到明显的黑素细胞活化，而成体中未见到这种情况。黑素细胞迁移至表皮基底层，其数量在UVR照射后3 - 5天达到峰值，随后减少。它们似乎起源于毛囊，通过外根鞘迁移至表皮。在黑素细胞特异性过表达Hras（G12V）的易患黑色素瘤小鼠中，与UVR处理的野生型小鼠相比，基底层黑素细胞的大小和树突状形态增加。携带pRb通路细胞周期缺陷（致癌性Cdk4（R24C））的小鼠中的黑素细胞对UVR未表现出如携带Hras（G12V）的小鼠那样增强的反应。新生小鼠黑素细胞对UVR诱导的增殖和迁移的高度敏感性可能部分解释了这种暴露形式在携带致癌突变的小鼠中诱导黑色素瘤的效用。
