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.
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.
Authors: Jesus M Banales; Vincenzo Cardinale; Guido Carpino; Marco Marzioni; Jesper B Andersen; Pietro Invernizzi; Guro E Lind; Trine Folseraas; Stuart J Forbes; Laura Fouassier; Andreas Geier; Diego F Calvisi; Joachim C Mertens; Michael Trauner; Antonio Benedetti; Luca Maroni; Javier Vaquero; Rocio I R Macias; Chiara Raggi; Maria J Perugorria; Eugenio Gaudio; Kirsten M Boberg; Jose J G Marin; Domenico Alvaro Journal: Nat Rev Gastroenterol Hepatol Date: 2016-04-20 Impact factor: 46.802
Authors: Suet Kee Loo; Megan E Yates; Sichun Yang; Steffi Oesterreich; Adrian V Lee; Xiao-Song Wang Journal: Genes Chromosomes Cancer Date: 2022-02-17 Impact factor: 5.006
Authors: Allison E Bridges; Sabarish Ramachandran; Kavin Tamizhmani; Utkarsh Parwal; Adrienne Lester; Pragya Rajpurohit; Daley S Morera; Sarrah L Hasanali; Pachiappan Arjunan; Ravirajsinh N Jedeja; Nikhil Patel; Pamela M Martin; Hasan Korkaya; Nagendra Singh; Santhakumar Manicassamy; Puttur D Prasad; Vinata B Lokeshwar; Bal L Lokeshwar; Vadivel Ganapathy; Muthusamy Thangaraju Journal: Mol Cancer Res Date: 2021-06-07 Impact factor: 5.852