HDM2 protein overexpression, but not gene amplification, is related to tumorigenesis of cutaneous melanoma.
HDM2 protein overexpression, but not gene amplification, is related to tumorigenesis of cutaneous melanoma.
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发表时间：
2001-10
期刊：
影响因子：
11.2
通讯作者：
D. Polsky;Boris C. Bastian;Carole Hazan;Kate Melzer;J. Pack;Alan N. Houghton;K. J. Busam;Carlos Cordon-Cardo;Iman Osman
中科院分区：
文献类型：
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作者：
D. Polsky;Boris C. Bastian;Carole Hazan;Kate Melzer;J. Pack;Alan N. Houghton;K. J. Busam;Carlos Cordon-Cardo;Iman Osman
我们研究了 HDM2（小鼠 mdm2 的人类同源物）的改变在皮肤黑色素瘤的肿瘤发生和进展中的作用。通过免疫组织化学和蛋白质印迹法检测 HDM2 蛋白表达，并通过 Southern 印迹 (SB) 或荧光原位杂交检测 HDM2 基因，对代表黑色素细胞转化谱中不同点的 172 例病例（16 例发育不良痣、11 例原位黑色素瘤、107 例侵袭性原发性病变和 38 例转移性病变）以及 11 种人类黑色素瘤细胞系进行了详细表征。放大。 HDM2 过表达（定义为显示核免疫反应性的 >20% 肿瘤细胞）在 16 个发育不良痣中的 1 个（6%）、11 个原位黑色素瘤中的 3 个（27%）以及 145 个侵袭性原发性和转移性黑色素瘤中的 81 个（56%）中观察到。在不同肿瘤厚度的侵袭性原发病例以及转移病例中观察到了相似的 HDM2 过表达频率：40 例中有 21 例（53%）肿瘤厚度为 4 mm； 38 例转移瘤中的 19 例 (50%)。使用荧光原位杂交在 88 个原发病例中观察到 1 个 (1%) 观察到 HDM2 扩增，使用 SB 在 12 个过表达 HDM2 的转移病例中观察到 0 个 (0%)。黑色素瘤细胞系表达 HDM2 蛋白，但没有 SB 扩增的证据。我们的数据表明 HDM2 蛋白过度表达在侵袭性和转移性黑色素瘤中很常见。在非侵袭性黑色素瘤中观察到 HDM2 过度表达表明该癌基因的表达可能在黑色素细胞转化中发挥早期作用。 HDM2 扩增很少发生，上调 HDM2 表达的其他机制正在研究中。
We investigated the role of alterations of HDM2, the human homologue of murine mdm2, in the tumorigenesis and progression of cutaneous melanoma. A well-characterized cohort of 172 cases representing different points in the spectrum of melanocyte transformation (16 dysplastic nevi, 11 melanomas in situ, 107 invasive primaries, and 38 metastatic lesions), as well as 11 human melanoma cell lines were examined by immunohistochemistry and Western blotting for HDM2 protein expression, and by either Southern blotting (SB) or fluorescence in situ hybridization for HDM2 gene amplification. HDM2 overexpression, defined as >20% tumor cells showing nuclear immunoreactivity, was observed in 1 of 16 (6%) dysplastic nevi, 3 of 11 (27%) melanomas in situ, and 81 of 145 (56%) invasive primary and metastatic melanomas. Comparable frequencies of HDM2 overexpression were observed among invasive primary cases with differing tumor thicknesses as well as among the metastatic cases: 21 of 40 (53%) at 4 mm; and 19 of 38 (50%) metastases. HDM2 amplification was observed in 1 of 88 (1%) primary cases using fluorescence in situ hybridization, and in 0 of 12 (0%) metastatic cases that overexpressed HDM2 using SB. Melanoma cell lines expressed HDM2 protein, but there was no evidence of amplification by SB. Our data suggest that HDM2 protein overexpression is common in invasive and metastatic melanoma. Observing HDM2 overexpression in noninvasive melanoma suggests that expression of this oncogene may play an early role in melanocyte transformation. HDM2 amplification occurs infrequently, and other mechanisms that up-regulate HDM2 expression are under investigation.