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Frequent inactivation of SPARC by promoter hypermethylation in colon cancers

Authors
 Eungi Yang  ;  Hyun Ju Kang  ;  Hoguen Kim  ;  Nam Kyu Kim  ;  Hwanseok Rhee  ;  Kwi Hye Koh 
Citation
 INTERNATIONAL JOURNAL OF CANCER, Vol.121(3) : 567-575, 2007 
Journal Title
 INTERNATIONAL JOURNAL OF CANCER 
ISSN
 0020-7136 
Issue Date
2007
MeSH
Azacitidine/analogs & derivatives ; Azacitidine/pharmacology ; Cell Line, Tumor ; Colonic Neoplasms/genetics* ; CpG Islands ; DNA Methylation* ; DNA, Neoplasm ; Decitabine ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Osteonectin/genetics* ; Prognosis ; Promoter Regions, Genetic* ; Survival Analysis
Abstract
Epigenetic modification of gene expression plays an important role in the development of human cancers. The inactivation of SPARC through CpG island methylation was studied in colon cancers using oligonucleotide microarray analysis and methylation specific PCR (MSP). Gene expression of 7 colon cancer cell lines was evaluated before and after treatment with the demethylating agent 5-aza-2′-deoxycytidine (5Aza-dC) by oligonucleotide microarray analysis. Expression of SPARC was further examined in colon cancer cell lines and primary colorectal cancers, and the methylation status of the SPARC promoter was determined by MSP. SPARC expression was undetectable in 5 of 7 (71%) colorectal cancer cell lines. Induction of SPARC was demonstrated after treatment with the demethylating agent 5Aza-dC in 5 of the 7 cell lines. We examined the methylation status of the CpG island of SPARC in 7 colon cancer cell lines and in 20 test set of colon cancer tissues. MSP demonstrated hypermethylation of the CpG island of SPARC in 6 of 7 cell lines and in all 20 primary colon cancers, when compared with only 3 of 20 normal colon mucosa. Immunohistochemical analysis showed that SPARC expression was downregulated or absent in 17 of 20 colon cancers. A survival analysis of 292 validation set of colorectal carcinoma patients revealed a poorer prognosis for patients lacking SPARC expression than for patients with normal SPARC expression (56.79% vs. 75.83% 5-year survival rate, p = 0.0014). The results indicate that epigenetic gene silencing of SPARC is frequent in colon cancers, and that inactivation of SPARC is related to rapid progression of colon cancers.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/ijc.22706/abstract
DOI
10.1002/ijc.22706
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Clinical Genetics (임상유전학과) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyun Ju(강현주)
Koh, Kwi Hye(고귀혜)
Kim, Nam Kyu(김남규) ORCID logo https://orcid.org/0000-0003-0639-5632
Kim, Hogeun(김호근)
Rhee, Hwan Seok(이환석)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96138
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