Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Pancreas Institute, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Cell Prolif. 2018 Jun;51(3):e12428. doi: 10.1111/cpr.12428. Epub 2017 Dec 20.
Thymidine kinase 1 (TK1) is one of the salvage enzymes engaged in the synthesis of DNA. Although a pro-carcinogenetic role of TK1 has been reported in various types of cancers, its role in pancreatic ductal adenocarcinoma (PDAC) is still unknown. The study is aimed to elaborate the function of TK1 in PDAC and the potential mechanisms in the following study.
TK1 expression was analysed by immunohistochemistry, real-time PCR and Western blot, and its relationship with clinicopathological characteristics of PDAC patients was further investigated. To verify the function of TK1 and potential mechanism, TK1 siRNA was used to transfect PDAC cells and performed a series of assays in cell and animal models.
The level of TK1 expression was higher in cancerous tissues compared with matched adjacent tissues. TK1 overexpression was associated with progression of PDAC and poor prognosis. Knockdown of TK1 could suppress cell proliferation via inducing S phase arrest mediated by upregulation of P21. Further mechanism investigation suggested that transcription factor E2F-1 could directly regulate the TK1 and promote tumour proliferation.
The results suggested that TK1 might be involved in the development and progression of PDAC by regulating cell proliferation and show that TK1 may work as a promising therapeutic target in patients with PDAC.
胸苷激酶 1（TK1）是参与 DNA 合成的补救酶之一。虽然在各种类型的癌症中已经报道了 TK1 的致癌前作用，但它在胰腺导管腺癌（PDAC）中的作用仍不清楚。本研究旨在阐述 TK1 在 PDAC 中的功能及其在以下研究中的潜在机制。
通过免疫组织化学、实时 PCR 和 Western blot 分析 TK1 的表达，并进一步研究其与 PDAC 患者临床病理特征的关系。为了验证 TK1 的功能和潜在机制，使用 TK1 siRNA 转染 PDAC 细胞，并在细胞和动物模型中进行了一系列实验。
与配对的相邻组织相比，癌组织中 TK1 的表达水平更高。TK1 的过表达与 PDAC 的进展和预后不良相关。TK1 的敲低可通过上调 P21 诱导 S 期阻滞来抑制细胞增殖。进一步的机制研究表明，转录因子 E2F-1 可以直接调节 TK1 并促进肿瘤增殖。
这些结果表明，TK1 可能通过调节细胞增殖参与 PDAC 的发生和发展，并表明 TK1 可能成为 PDAC 患者有前途的治疗靶点。
