論文 - 詳細
| RRC ID | 43291 |
|---|---|
| 著者 | Obama K, Satoh S, Hamamoto R, Sakai Y, Nakamura Y, Furukawa Y. |
| タイトル | Enhanced expression of RAD51 associating protein-1 is involved in the growth of intrahepatic cholangiocarcinoma cells. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE:Intrahepatic cholangiocarcinoma (ICC) is the second most common primary cancer in the liver, and its incidence is increasing in developed countries. EXPERIMENTAL DESIGN:To discover novel molecular targets for the diagnosis and treatment of ICCs, we earlier analyzed expression profiles of 25 ICCs using a cDNA microarray containing 27,648 genes. In this study, we focused on the RAD51 associating protein-1 (RAD51AP1) gene because its expression was frequently elevated in our microarray data. RESULTS:Quantitative PCR confirmed that RAD51AP1 expression was elevated in the great majority of the ICCs examined. Immunohistochemical analysis with anti-RAD51AP1 antibody further corroborated its accumulation in 14 of 23 ICC tissues (61%). Notably, suppression of RAD51AP1 by short interfering RNA resulted in growth suppression of cholangiocarcinoma cells, suggesting its involvement in the development and/or progression of ICC. Because RAD51AP1 interacts with RAD51, a molecule involved in DNA repair, we investigated whether RAD51AP1 is implicated in DNA strand breaks using gamma-irradiation. As a result, gamma-irradiation augmented RAD51AP1 protein expression and brought a focus formation in the nuclei, where accumulated RAD51AP1 colocalized with phosphorylated histone 2AX (gamma-H2AX) and RAD51. These data suggest that RAD51AP1 may play a role in cell proliferation as well as DNA repair. CONCLUSION:Our findings may contribute to the better understanding of cholangiocarcinogenesis and open a new avenue to the development of novel therapeutic and/or diagnostic approach to this type of tumor. |
| 巻・号 | 14(5) |
| ページ | 1333-9 |
| 公開日 | 2008-3-1 |
| DOI | 10.1158/1078-0432.CCR-07-1381 |
| PII | 14/5/1333 |
| PMID | 18316552 |
| MeSH | Animals Bile Duct Neoplasms / genetics* Bile Duct Neoplasms / pathology* Bile Ducts, Intrahepatic / pathology* Blotting, Northern Blotting, Western Cell Differentiation Cell Proliferation* Cholangiocarcinoma / genetics* Cholangiocarcinoma / pathology* DNA Primers / chemistry DNA Repair DNA-Binding Proteins / genetics* Gamma Rays Gene Expression Profiling Humans Immunoenzyme Techniques Middle Aged Oligonucleotide Array Sequence Analysis RNA, Messenger / genetics RNA, Messenger / metabolism RNA-Binding Proteins Rabbits Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured / radiation effects |
| IF | 10.107 |
| 引用数 | 18 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RBE(RCB1292) SSP-25(RCB1293) |