Zhang Hong, Rosdahl Inger
Department of Dermatology, Institute of Biomedicine and Surgery, Linköping University, SE-581 85 Linköping, Sweden.
Carcinogenesis. 2003 Dec;24(12):1929-34. doi: 10.1093/carcin/bgg171. Epub 2003 Sep 26.
Ultraviolet (UV) irradiation has been involved in both initiation and promotion of carcinogenesis in melanoma. Alterations of cellular proliferation proteins, such as p73, Nup88, Id1 and p27 have been considered to play critical roles in melanoma development. However, the molecular mechanisms behind melanoma carcinogenesis are still poorly understood. In this study, we used human skin melanocytes as an experimental model system to investigate effects of UV irradiation on protein expression concerning cellular proliferation. The melanocytes prepared from human foreskin were separately exposed to various doses of UVA or UVB and post-cultivated for 24 or 48 h. Total proteins were isolated from the melanocytes, and expression of p73, Nup88, Id1, p27, bcl-2 and proliferating cell nuclear antigen (PCNA) proteins was examined by western blotting and immunocytochemistry. Results showed that expression of p73 and Nup88 was enhanced by UVA irradiation in a dose- and time-dependent manner. However, expression of Id1, p27, bcl-2 and PCNA proteins was not changed upon exposure to the UVA. Id1 and p27 proteins were over-expressed by exposure to UVB, but expression of p73, Nup88, bcl-2 and PCNA proteins was not changed by the UVB irradiation. The data suggested that UVA and UVB irradiation might lead to alterations of the different intracellular proteins. UVA enhanced protein expression concerning cell growth (p73 and Nup88) and UVB might over-express proteins concerning cellular proliferation (Id1 and p27). UVA and UVB may induce initiation of melanoma via separate intracellular pathways.
紫外线(UV)照射与黑色素瘤致癌过程的起始和促进均有关联。细胞增殖蛋白的改变,如p73、Nup88、Id1和p27,被认为在黑色素瘤发展中起关键作用。然而,黑色素瘤致癌背后的分子机制仍知之甚少。在本研究中,我们使用人皮肤黑素细胞作为实验模型系统,来研究紫外线照射对细胞增殖相关蛋白表达的影响。从人包皮制备的黑素细胞分别暴露于不同剂量的UVA或UVB,并在照射后培养24或48小时。从黑素细胞中分离总蛋白,通过蛋白质印迹法和免疫细胞化学检测p73、Nup88、Id1、p27、bcl-2和增殖细胞核抗原(PCNA)蛋白的表达。结果显示,UVA照射以剂量和时间依赖性方式增强了p73和Nup88的表达。然而,暴露于UVA后,Id1、p27、bcl-2和PCNA蛋白的表达未发生变化。暴露于UVB会使Id1和p27蛋白过表达,但UVB照射不会改变p73、Nup88、bcl-2和PCNA蛋白的表达。数据表明,UVA和UVB照射可能导致不同细胞内蛋白的改变。UVA增强了与细胞生长相关的蛋白表达(p73和Nup88),而UVB可能使与细胞增殖相关的蛋白过表达(Id1和p27)。UVA和UVB可能通过不同的细胞内途径诱导黑色素瘤的起始。