Reference - Detail
|Author||Obama K, Satoh S, Hamamoto R, Sakai Y, Nakamura Y, Furukawa Y.|
|Title||Enhanced expression of RAD51 associating protein-1 is involved in the growth of intrahepatic cholangiocarcinoma cells.|
|Journal||Clin Cancer Res|
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.
|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 Rabbits Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured / radiation effects|
|Human and Animal Cells|