Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul.
APMIS. 2011 Nov;119(11):802-7. doi: 10.1111/j.1600-0463.2011.02812.x. Epub 2011 Sep 22.
Autophagy is an evolutionarily conserved mechanism that plays important roles in both cell death and cell survival. ATG5 is an essential constituent for autophagosome formation, which sequesters cytoplasmic materials before lysosomal delivery. Although both cell death and survival are important in cancer development, the role of autophagy in prostate cancer development remains unclear. The aim of this study was to see whether alterations of ATG5 protein expression and somatic mutations of the ATG5 gene are found in prostate cancers. In the present study, we analyzed ATG5 protein expression in 107 prostate carcinomas by immunohistochemistry; additionally, we assayed the presence of ATG5 somatic mutations in 45 prostate carcinomas by single-strand conformation polymorphism. Immunostaining of ATG5 in normal prostate cells was observed in 44.9% of the cases, whereas in prostate intraepithelial neoplasm (PIN) and prostate cancer cells, ATG5 was observed in 100% and 89.7% of the cases, respectively. Cytoplasmic expression of ATG5 that might be related to autophagy was seen in PIN (100%) and cancers (83.2%), but not in normal cells (0%). ATG5 expression was not associated with any of the pathologic characteristics, including size of the cancers, age, Gleason score, and stage. As for the ATG5 gene, we found no somatic mutations in the prostate cancers. In this study, we analyzed ATG5 expression and mutation in prostate cancers, and found that ATG5 expression was altered in prostate cancers. The expression of ATG5, especially in the cytoplasm, in the prostate cancers compared with normal prostate cells suggested that overexpression of this protein may be related to autophagy and might play a role in prostate tumorigenesis.
自噬是一种进化上保守的机制，在细胞死亡和细胞存活中都发挥着重要作用。ATG5 是自噬体形成的必需组成部分，它在溶酶体传递之前隔离细胞质物质。尽管细胞死亡和存活在癌症发展中都很重要，但自噬在前列腺癌发展中的作用仍不清楚。本研究旨在观察 ATG5 蛋白表达的改变和 ATG5 基因的体细胞突变是否存在于前列腺癌中。在本研究中，我们通过免疫组织化学分析了 107 例前列腺癌中的 ATG5 蛋白表达；此外，我们通过单链构象多态性检测了 45 例前列腺癌中 ATG5 体细胞突变的存在。在正常前列腺细胞中观察到 ATG5 的免疫染色，在前列腺上皮内瘤变（PIN）和前列腺癌细胞中，ATG5 的免疫染色分别在 100%和 89.7%的病例中观察到。可能与自噬有关的 ATG5 细胞质表达在 PIN（100%）和癌症（83.2%）中可见，但在正常细胞（0%）中不可见。ATG5 表达与任何病理特征无关，包括癌症的大小、年龄、Gleason 评分和分期。至于 ATG5 基因，我们在前列腺癌中未发现体细胞突变。在本研究中，我们分析了前列腺癌中的 ATG5 表达和突变，发现 ATG5 在前列腺癌中表达改变。与正常前列腺细胞相比，前列腺癌细胞中 ATG5 的表达（特别是细胞质中的表达）表明该蛋白的过表达可能与自噬有关，并可能在前列腺肿瘤发生中发挥作用。
