Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions
Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions
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DOI：
10.1016/j.humpath.2009.09.004
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发表时间：
2010-04-01
期刊：
影响因子：
3.3
通讯作者：
Massi, Daniela
中科院分区：
文献类型：
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作者：
Miracco, Clelia;Cevenini, Gabriele;Massi, Daniela
Beclin 1和LC 3自噬基因在几种人类癌症类型中发生改变。本研究旨在评估Beclin 1和LC 3在皮肤黑素细胞病变中的表达，其中尚未对其进行研究。在黑色素瘤中，我们将它们的表达与传统的组织病理学预后因素相关联。在149个病变，包括良性痣，发育不良痣，放射状生长期黑色素瘤，垂直生长期黑色素瘤，黑色素瘤转移瘤，蛋白质进行了评价，通过免疫组化，并在良性痣，垂直生长期黑色素瘤和黑色素瘤转移瘤的代表性病例进行了评价，通过蛋白质印迹。在大多数病变中，信使RNA水平也通过实时逆转录聚合酶链反应进行了评估。两种基因在所有研究条件下均表达。Beclin 1胞浆蛋白和信使RNA以及LC 3信使RNA随着肿瘤进展而显着下降（P < .05）。Beclin 1胞浆高表达的比例从良性痣的100%下降到发育不良痣的86.4%，放射状生长期黑素瘤的54.5%，垂直生长期黑素瘤的54.3%，以及黑素瘤转移的26.7%。LC 3 II蛋白在黑色素瘤转移灶中表达最低（53.3%）（P <0.05）;然而，LC 3 II蛋白在几种非良性病变中过表达，在放射状生长期黑色素瘤中比例最高（45.5%）。LC 3 II蛋白表达与厚度、溃疡和有丝分裂率呈负相关。在多变量分析中，两个基因的信使RNA区分非恶性（良性和发育不良痣）和恶性（放射状，垂直生长期黑色素瘤和黑色素瘤转移）病变。因此，我们的研究结果表明，Beclin 1和LC 3 II自噬基因的表达也改变了黑素细胞肿瘤。(C)2010年爱思唯尔公司All rights reserved.
Beclin 1 and LC3 autophagic genes are altered in several human cancer types. This study was designed to assess the expression of Beclin 1 and LC3 in cutaneous melanocytic lesions, in which they have not yet been investigated. In melanoma, we correlated their expression with conventional histopathologic prognostic factors. In 149 lesions, including benign nevi, dysplastic nevi, radial growth phase melanomas, vertical growth phase melanomas, and melanoma metastases, proteins were evaluated by immunohistochemistry, and, in representative cases of benign nevi, vertical growth phase melanomas and melanoma metastases were evaluated by Western blotting. In most lesions, messenger RNA level was also assessed by real-time reverse transcriptase polymerase chain reaction. Both genes were expressed in all the investigated conditions. Beclin 1 cytoplasmic protein and messenger RNA, as well as LC3 messenger RNA, significantly decreased with tumor progression (P < .05). The percentage of cases with high cytoplasmic expression of beclin 1 from 100% in benign nevi declined to 86.4% in dysplastic nevi, 54.5% in radial growth phase melanomas, 54.3% in vertical growth phase melanomas, and 26.7% in melanoma metastases. The lowest expression of LC3 II protein was observed in melanoma metastases (53.3% of cases) (P < .05); LC3 II protein overexpression was, however, found in several nonbenign lesions, with the highest percentage (45.5%) in radial growth phase melanomas. LC3 II protein expression was inversely correlated to thickness, ulceration, and mitotic rate. In a multivariate analysis, messenger RNAs for both genes discriminated between nonmalignant (benign and dysplastic nevi) and malignant (radial, vertical growth phase melanomas, and melanoma metastases) lesions. Our results, therefore, indicate that beclin 1 and LC3 II autophagic gene expression is altered also in melanocytic neoplasms. (C) 2010 Elsevier Inc. All rights reserved.