Departments of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea.
Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Republic of Korea.
Genes Genomics. 2019 Nov;41(11):1293-1299. doi: 10.1007/s13258-019-00858-y. Epub 2019 Aug 6.
Hypomethylation of long interspersed nuclear element-1 (LINE-1) is closely related to certain cancers and concerns with aggressive tumor behavior. Previously, we reported LINE-1 open reading frame-1 (ORF1) protein level was significantly up-regulated in ovarian cancers compared with normal ovary. Hypomethylation of local LINE-1 sequence has been reported to reactivate MET proto-oncogene in colon cancers and hepatocellular carcinoma. However, the relationship between LINE-1 and c-MET expressions in ovarian cancer is not yet studied.
Here, we analyzed the expression patterns of LINE-1 ORF1 and c-Met protein in ovarian cancer tissue microarrays containing 208 surgical specimens including normal ovary and malignant ovarian cancers.
The expressions of both LINE-1 ORF1 and c-Met protein were significantly increased in ovarian cancers and peaked in early stage of tumor. Other clinical data including age and tumor types were not significantly related with both proteins. Co-relationship between LINE-1 ORF1 and c-Met protein was significant (p = 0.03) but several patients show different expression patterns.
These results propose that LINE-1 ORF1 significantly activates c-Met but not in all cases, suggesting other factors may be involved simultaneously.
长散布核元件-1(LINE-1)的低甲基化与某些癌症密切相关,并与侵袭性肿瘤行为有关。此前,我们报道LINE-1 开放阅读框-1(ORF1)蛋白水平在卵巢癌中明显高于正常卵巢。局部 LINE-1 序列的低甲基化已被报道可重新激活结肠癌和肝细胞癌中的 MET 原癌基因。然而,LINE-1 与卵巢癌中 c-MET 表达之间的关系尚未研究。
在这里,我们分析了含有 208 例手术标本的卵巢癌组织微阵列中 LINE-1 ORF1 和 c-Met 蛋白的表达模式,包括正常卵巢和恶性卵巢癌。
卵巢癌中 LINE-1 ORF1 和 c-Met 蛋白的表达均显著增加,并在肿瘤早期达到高峰。其他临床数据,包括年龄和肿瘤类型,与这两种蛋白均无显著相关性。LINE-1 ORF1 和 c-Met 蛋白之间存在显著的相关性(p=0.03),但有几个患者表现出不同的表达模式。
这些结果表明,LINE-1 ORF1 显著激活 c-Met,但并非在所有情况下都是如此,提示同时可能涉及其他因素。