Kim JY, Kim HJ, Park JH, Park DI, Cho YK, Sohn CI, Jeon WK, Kim BI, Kim DH, Chae SW, Sohn JH. Epidermal growth factor upregulates Skp2/Cks1 and p27kip1 in human extrahepatic cholangiocarcinoma cells. World J Gastroenterol 2014; 20(3): 755-773 [PMID: 24574749 DOI: 10.3748/wjg.v20.i3.755]
Corresponding Author of This Article
Hong Joo Kim, MD, Department of Internal Medicine, Sungkyunkwan University Kangbuk Samsung Hospital, 108, Pyung-Dong, Jongro-Ku, Seoul 110-746, South Korea. hongjoo3.kim@samsung.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Original Article
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World J Gastroenterol. Jan 21, 2014; 20(3): 755-773 Published online Jan 21, 2014. doi: 10.3748/wjg.v20.i3.755
Epidermal growth factor upregulates Skp2/Cks1 and p27kip1 in human extrahepatic cholangiocarcinoma cells
Ja-yeon Kim, Hong Joo Kim, Jung Ho Park, Dong Il Park, Yong Kyun Cho, Chong Il Sohn, Woo Kyu Jeon, Byung Ik Kim, Dong Hoon Kim, Seoung Wan Chae, Jin Hee Sohn
Ja-yeon Kim, Kangbuk Samsung Medical Research Institute, Sungkyunkwan University Kangbuk Samsung Hospital, Seoul 110-746, South Korea
Hong Joo Kim, Jung Ho Park, Dong Il Park, Yong Kyun Cho, Chong Il Sohn, Woo Kyu Jeon, Byung Ik Kim, Department of Internal Medicine, Sungkyunkwan University Kangbuk Samsung Hospital, Seoul 110-746, South Korea
Dong Hoon Kim, Seoung Wan Chae, Jin Hee Sohn, Department of Pathology, Sungkyunkwan University Kangbuk Samsung Hospital, Seoul 110-746, South Korea
Author contributions: Kim J and Kim HJ contributed to conception and design, performing of molecular biologic experiments, analysis and interpretation of the data, drafting the manuscript, critical revision of the manuscript for important intellectual content, and final approval of the manuscript; Park JH, Park DI, Sohn CI, Cho YK, Jeon WK and Kim BI contributed to critical revisions of the manuscript for important intellectual content and final approval of the manuscript; Kim DH, Chae SW and Sohn JH contributed to the performing and interpretation of the immunohistochemical stains using the relevant microarray tissue blocks of cholangiocarcinomas.
Supported by A grant from Samsung Biomedical Research Institute, No. C-A9-210-1
Correspondence to: Hong Joo Kim, MD, Department of Internal Medicine, Sungkyunkwan University Kangbuk Samsung Hospital, 108, Pyung-Dong, Jongro-Ku, Seoul 110-746, South Korea. hongjoo3.kim@samsung.com
Telephone: +82-2-20012060 Fax: +82-2-2-20012049
Received: July 13, 2013 Revised: September 27, 2013 Accepted: November 2, 2013 Published online: January 21, 2014
Core Tip
Core tip: Based on the idea that S-phase kinase-associated protein 2 (Skp2) and p27kip1 might play a role in the pathogenesis and disease progression of patients with extrahepatic cholangiocarcinoma, immunohistochemical staining for Skp2, cyclin-dependent kinases regulatory subunit 1 (Cks1), p27kip1, and Ki67, along with other relevant molecular biologic experiments, were performed in tissue samples and human cholangiocarcinoma cell lines. Higher immunostaining intensity of Skp2 was an independent prognostic factor in patients with extrahepatic cholangiocarcinoma, and exogenous epidermal growth factor upregulates mRNA and protein levels of Skp2/Cks1 and p27kip1 in SNU-1196, SNU-1079, and SNU-245 cells. By chromatin immunoprecipitation assay, we found that E2F1 transcription factor directly binds to the promoter site of Skp2.
