High promoter activity of cytokeratin‑19 gene in cholangiocarcinoma

Qin,Jian; Wang,Min; Qin,Jun; Cai,Qu; Peng,Zhi‑Hai

doi:10.3892/mco.2018.1700

High promoter activity of cytokeratin‑19 gene in cholangiocarcinoma

Authors:
- Jian Qin
- Min Wang
- Jun Qin
- Qu Cai
- Zhi‑Hai Peng
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Affiliations: Department of Surgery, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, P.R. China, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Published online on: August 16, 2018 https://doi.org/10.3892/mco.2018.1700
Pages: 467-471

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Abstract

Conditionally replicating adenoviral vectors constructed with tumor‑specific promoters (TSPs) offers a viable tool for the treatment of cholangiocarcinoma. The aim of the present study was to investigate cholangiocarcinoma‑specific TSPs that remain active in adenoviral constructs in gene therapy. The mRNA expressions of cyclooxygenase‑2, cytokeratin‑19 (CK19), mucin‑1, midkine and telomerase reverse transcriptase were determined in human cholangiocarcinoma cell lines, primary human hepatocytes and cholangiocytes using reverse transcription‑quantitative polymerase chain reaction. The candidate promoters constructed in adenoviral vectors were analyzed for their activities in cholangiocarcinoma cell lines, primary human hepatocytes and cholangiocytes using dual‑luciferase reporter assays. The mRNA expression of CK19 was markedly higher in the QBC939 cell line, indicating specificity to cholangiocarcinoma. Moreover, the promoter activity of CK19 in the adenoviral vector in infected cholangiocarcinoma cells was found to be significantly stronger compared with that in infected primary human hepatocytes and cholangiocytes. CK19 may be implicated in the pathogenesis of cholangiocarcinoma, as demonstrated by the stronger activity of its promoter, as well as the higher expression of mRNA in tumor cells. Therefore, the use of the promoter sequence of the CK19 gene may represent a potential tool in cholangiocarcinoma‑specific adenoviral gene therapy.

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