Increased expression of germinal center-associated nuclear protein (GANP) is associated with malignant transformation of melanocytes
Increased expression of germinal center-associated nuclear protein (GANP) is associated with malignant transformation of melanocytes
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DOI：
10.1016/j.jdermsci.2005.12.007
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发表时间：
2006-04-01
影响因子：
4.6
通讯作者：
Sakaguchi, N
中科院分区：
文献类型：
--
作者：
Kageshita, T;Kuwahara, K;Sakaguchi, N
背景：生发中心相关核蛋白（Germinal center associated nuclear protein， GANP）是一种在生发中心B细胞中上调表达的新克隆分子。尽管GANP在B细胞复制和存活过程中调控DNA修复，但对其在黑色素细胞中的表达知之甚少。目的：探讨GANP和磷酸化GANP （P-GANP）是否在培养的人黑色素细胞和黑色素瘤细胞以及良性和恶性黑色素细胞病变中表达。此外，我们的目的是确定GANP和P-GANP是否与黑素细胞谱系的恶性转化有关。方法：采用免疫染色法和体外激酶法分析体外培养黑色素细胞中GANP和P-GANP的表达。免疫组织化学分析黑色素细胞病变中GANP和P-GANP的表达。结果：与黑色素细胞相比，培养的黑色素瘤细胞中GANP和P-GANP表达上调。GANP和P-GANP局限于黑素细胞核，但在黑色素瘤细胞的细胞质中共表达。另一方面，GANP和P-GANP在黑素细胞痣和黑色素瘤病变中广泛不同水平表达，呈核和细胞质染色模式。黑色素瘤细胞的GANP和P-GANP染色强度高于黑色素细胞痣细胞，但原发性黑色素瘤病变的染色强度与任何临床病理变量无关。细胞质GANP和P-GANP的表达与MCM3和Ki67的表达相关。结论：这些数据首次表明，与黑色素细胞相比，GANP和P-GANP在培养的黑色素瘤细胞中表达上调，并且在良恶性黑色素细胞肿瘤细胞中广泛表达。(c) 2005年日本皮肤病学调查学会。爱思唯尔爱尔兰有限公司出版。版权所有。
Background: Germinal center-associated nuclear protein (GANP) is a newly cloned molecule that is up-regulated in the germinal center B cells. Although GANP functions in the regulation of DNA repair during replication and survival of B cells, little is known about its expression in melanocytic cells.Objectives: To investigate whether GANP and phosphorylated-GANP (P-GANP) are expressed in cultured human melanocytes and melanoma cells and in benign and malignant melanocytic lesions. In addition, we aim to determine whether GANP and P-GANP are associated with malignant transformation of melanocytic lineage.Methods: GANP and P-GANP expression in cultured melanocytic cells was analyzed by immunostaining and in vitro kinase assay. GANP and P-GANP expression in melanocytic lesions was analyzed by immunohistochemistry.Results: GANP and P-GANP were up-regulated in cultured melanoma cells compared to melanocytes. GANP and P-GANP were restricted to nucleus of melanocytes but co-expressed in cytoplasm of melanoma cells. On the other hand, GANP and P-GANP were widely expressed at various levels in melanocytic nevi and melanoma lesions with nuclear and cytoplasmic staining pattern. Melanoma cells showed a stronger intensity of GANP and P-GANP than melanocytic nevus cells, however the staining intensity in primary melanoma lesions was not associated with any clinicopathological variables. Cytoplasmic GANP and P-GANP expression was associated with MCM3 and Ki67 expression.Conclusions: These data suggest, for the first time, that GANP and P-GANP are upregulated in cultured melanoma cells compared to melanocytes and also they are widely expressed in benign and malignant melanocytic tumor cells. (c) 2005 Japanese Society for Investigative Dermatotogy. Published by Elsevier Ireland Ltd. All rights reserved.