Reference - Detail
| RRC ID | 44759 |
|---|---|
| Author | Nakagawa S, Okabe H, Sakamoto Y, Hayashi H, Hashimoto D, Yokoyama N, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Chikamoto A, Watanabe M, Beppu T, Baba H. |
| Title | Enhancer of zeste homolog 2 (EZH2) promotes progression of cholangiocarcinoma cells by regulating cell cycle and apoptosis. |
| Journal | Ann Surg Oncol |
| Abstract |
BACKGROUND:Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2). When present in PRC2, EZH2 catalyzes trimethylation on lysine 27 residue of histone H3, resulting in epigenetic silencing of gene expression and cancer progression. We investigated the expression and function of EZH2 in intrahepatic and extrahepatic cholangiocarcinoma (ICC and ECC). METHODS:The influence of EZH2 on cell growth and apoptosis was assessed by knockdown experiments. Target gene of EZH2 was searched by quantitative RT-PCR. Clinical significance of EZH2 in 86 cholangiocarcinoma patients (45 ICC and 41 ECC) who underwent curative surgery was examined by immunohistochemistry. RESULTS:In vitro analysis, knockdown of EZH2 reduced cell growth, induced G1 arrest, and induced apoptosis, as confirmed by Annexin V staining and increased sub-G1 populations in cholangiocarcinoma cell lines. The expression levels of p16 (INK4a) and p27 (KIP1) were remarkably increased by knockdown of EZH2 in these cell lines. In immunohistochemical study, EZH2 upregulation correlated with tumor diameter (p = 0.0103) in ICC, lymph node metastasis (p = 0.0292) in ECC, and Ki67 index in both ICC (p = 0.0364) and ECC (p = 0.0017). In addition, EZH2 expression was correlated with poor prognosis in both ICC (p = 0.0447) and ECC (p = 0.0227). CONCLUSIONS:The current study demonstrated relationships between EZH2 expression and acceleration of the cell cycle and antiapoptosis, and poor prognosis in cholangiocarcinoma. These results suggest that EZH2 may represent a potential therapeutic target in patients with cholangiocarcinoma. |
| Volume | 20 Suppl 3 |
| Pages | S667-75 |
| Published | 2013-12-1 |
| DOI | 10.1245/s10434-013-3135-y |
| PMID | 23887863 |
| MeSH | Aged Apoptosis* Bile Duct Neoplasms / metabolism Bile Duct Neoplasms / mortality Bile Duct Neoplasms / secondary* Bile Ducts, Extrahepatic* Bile Ducts, Intrahepatic* Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Cycle* Cell Proliferation Cholangiocarcinoma / metabolism Cholangiocarcinoma / mortality Cholangiocarcinoma / pathology* Disease Progression Enhancer of Zeste Homolog 2 Protein Female Flow Cytometry Follow-Up Studies Humans Immunoenzyme Techniques Lymphatic Metastasis Male Neoplasm Staging Polycomb Repressive Complex 2 / antagonists & inhibitors Polycomb Repressive Complex 2 / genetics Polycomb Repressive Complex 2 / metabolism* Prognosis RNA, Messenger / genetics RNA, Small Interfering / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Survival Rate Tumor Cells, Cultured |
| IF | 3.153 |
| Times Cited | 21 |
| WOS Category | MEDICINE, RESEARCH & EXPERIMENTAL TRANSPLANTATION HEMATOLOGY CELL & TISSUE ENGINEERING |
| Resource | |
| Human and Animal Cells | RBE TFK-1 SSP-25 YSCCC |