PloS one, 2014-02, Vol.9 (2), p.e90247-e90247
2014
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- Autor(en) / Beteiligte
- Titel
- High expression of protein tyrosine kinase 7 significantly associates with invasiveness and poor prognosis in intrahepatic cholangiocarcinoma
- Ist Teil von
- PloS one, 2014-02, Vol.9 (2), p.e90247-e90247
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- The incidence, prevalence, and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. Protein tyrosine kinase-7 (PTK7) is upregulated in many common human cancers. However, its expression in ICC has not been studied. The present study aimed to explore the underlying mechanism of PTK7 in ICC. The role of PTK7 was studied in vitro by suppressing PTK7 expression in ICC cell lines. The in vivo effect of PTK7 was evaluated using a nude mouse model inoculated with a human ICC cell line. We also examined the role of PTK7 in human ICC samples. Cells with high PTK7 expression exhibited higher proliferation, DNA synthesis, invasion, and migration abilities than did cells with low PTK7 expression. The knockdown of PTK7 with small interfering RNA (siRNA) in high PTK7 expressing cells resulted in impairment of invasion, migration, and DNA synthesis through the regulation of several cell-cycle-related proteins. It also induced cell apoptosis and decreased phospho-RhoA expression. In a xenograft nude mouse model, PTK7 siRNA resulted in a reduction of the tumor size, compared with scrambled siRNA injection. PTK7 expression was higher in human ICC than in the normal bile duct. Patients with low expression of PTK7 had a longer disease-free survival and overall survival than those with high expression. PTK7 expression plays an important role in the invasiveness of ICC cells and leads to a poor prognosis in ICC patients. Thus, PTK7 can be used as a prognostic indicator, and the inhibition of PTK7 expression could be a new therapeutic target for ICC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0090247Titel-ID: cdi_plos_journals_1503272378
- Format
- –
- Schlagworte
- Adult, Aged, Aged, 80 and over, Analysis, Animals, Apoptosis, Bile Duct Neoplasms - genetics, Bile Duct Neoplasms - metabolism, Bile Duct Neoplasms - pathology, Bile ducts, Bile Ducts, Intrahepatic - metabolism, Bile Ducts, Intrahepatic - pathology, Biliary tract cancer, Biology, Cell Adhesion Molecules - genetics, Cell Adhesion Molecules - metabolism, Cell Cycle, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Cell growth, Cell Line, Tumor, Cell migration, Cell Movement, Cell proliferation, Cholangiocarcinoma, Cholangiocarcinoma - genetics, Cholangiocarcinoma - metabolism, Cholangiocarcinoma - pathology, Chromosomes, Colorectal cancer, Deoxyribonucleic acid, Digital cameras, DNA, DNA biosynthesis, DNA synthesis, Female, Gene expression, Gene Expression Regulation, Neoplastic, Health aspects, Hospitals, Humans, Invasiveness, Kinases, Male, Medical prognosis, Medicine, Membranes, Mice, Mice, Nude, Middle Aged, Neoplasm Invasiveness, Neoplasm Transplantation, Pathology, Patients, Phenols (Class of compounds), Polymerase chain reaction, Prognosis, Protein-tyrosine kinase, Proteins, Receptor Protein-Tyrosine Kinases - antagonists & inhibitors, Receptor Protein-Tyrosine Kinases - genetics, Receptor Protein-Tyrosine Kinases - metabolism, Review boards, rho GTP-Binding Proteins - genetics, rho GTP-Binding Proteins - metabolism, RhoA protein, Ribonucleic acid, RNA, RNA, Small Interfering - genetics, RNA, Small Interfering - metabolism, Signal Transduction, siRNA, Surgery, Survival, Synthesis, Tyrosine, Xenografts