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Differential Expression of CD133 Based on Microsatellite Instability Status in Human Colorectal Cancer

Authors
 Jae Jun Park  ;  Ji-hee Kwon  ;  Sun-Hee Oh  ;  Junjeong Choi  ;  Chang Mo Moon  ;  Joong Bae Ahn  ;  Sung Pil Hong  ;  Jae Hee Cheon  ;  Tae Il Kim  ;  Hoguen Kim  ;  Won Ho Kim 
Citation
 MOLECULAR CARCINOGENESIS, Vol.53(S1) : 1-10, 2014 
Journal Title
 MOLECULAR CARCINOGENESIS 
ISSN
 0899-1987 
Issue Date
2014
MeSH
AC133 Antigen ; Antigens, CD/metabolism* ; Blotting, Western ; Cell Adhesion Molecules, Neuronal/metabolism* ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism* ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/pathology ; Female ; Fetal Proteins/metabolism* ; Flow Cytometry ; Glycoproteins/metabolism* ; Humans ; Hyaluronan Receptors/metabolism* ; Immunoenzyme Techniques ; Male ; Microsatellite Instability* ; Middle Aged ; Mutation/genetics ; Neoplasm Staging ; Peptides/metabolism* ; Prognosis ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Tumor Cells, Cultured ; ras Proteins/genetics
Keywords
CD133 ; cancer stem cell ; colorectal cancer ; microsatellite instability
Abstract
The association between the types of genomic instability and cancer stem cell (CSC) has not been elucidated. We aimed to investigate the expressions of CSC markers with respect to microsatellite instability (MSI) status in human colorectal cancer (CRC). Immunostainings for CD133, CD44, and CD166, and K-ras mutation analysis were performed on 50 MSI-high (MSI-H), and 50 microsatellite stable (MSS) CRC tissues. In 11 MSS and MSI-H CRC cell lines, CD133 expression and DNA methylation statuses of the CD133 promoter were determined. The proportion of CD133 positive cells and the ability of colosphere formation were compared between HCT116 cells and HCT116 + Chr3 cells (hMLH1-restored HCT116 cells). Immunohistochemistry for CSC markers revealed that high CD133 expression was more frequent in MSS cancers than in MSI-H (P < 0.001, 74.0% vs. 28.0%, respectively), and related with short disease-free survival. Neither CD44 nor CD166 expression differed significantly with respect to MSI status. K-ras mutation showed no association with expressions of CD133, CD44, or CD166. CD133 expression was relatively high in the MSS cell lines compared to those in MSI-H, and showed a reverse correlation with DNA methylation of the CD133 promoter. hMLH1-restored HCT116 cells increased proportions of CD133 positive cells and colosphere forming ability, compared to those in HCT116 cells. In conclusion, high levels of CD133 expression were observed more frequently in MSS CRC than in MSI-H, suggesting that differential expression of colon CSC markers may be linked to tumor characteristics dependent on MSI status.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/mc.21971/abstract
DOI
10.1002/mc.21971
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kwon. Ji Hee(권지희)
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Kim, Ho Keun(김호근)
Moon, Chang Mo(문창모)
Park, Jae Jun(박재준)
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
Hong, Sung Pil(홍성필)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/97922
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