Effects of Chromosomal Polyploidy on Survival of Colon Cancer Cells.
10.4166/kjg.2011.57.3.150
- Author:
Sang Un PARK
1
;
Eun Sook CHOI
;
Yeon Sil JANG
;
Seung Hee HONG
;
In Hoo KIM
;
Dong Kyung CHANG
Author Information
1. Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. dkchang@skku.edu
- Publication Type:Original Article ; English Abstract ; Research Support, Non-U.S. Gov't
- Keywords:
Tetraploidy;
Chromosomal instability;
Aneuploidy;
Hydrogen peroxide
- MeSH:
Apoptosis;
Cell Division;
Cell Line, Tumor;
Cell Survival;
Chromosomal Instability;
Colonic Neoplasms/*genetics/metabolism;
Cyclin-Dependent Kinase Inhibitor p21/metabolism;
G2 Phase;
Humans;
Hydrogen Peroxide/toxicity;
Oxidative Stress;
*Polyploidy;
Tumor Suppressor Protein p53/metabolism
- From:The Korean Journal of Gastroenterology
2011;57(3):150-157
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND/AIMS: Tetraploid cells are frequently observed in the inflamed mucosal epithelial cells of the patients with Barrett's esophagus or chronic ulcerative colitis. Polyploidy often occurs during cell fusion, abortive cell cycle, and endoreplication. Most tetraploid cells are engaged to apoptotic pathway, but some remaining stable tetraploid cells consequently cause aneuploidization and chromosomal instability. We investigated whether tetraploid cells could acquire survival advantage and hold a dominant position for natural selection. METHODS: We established tetraploid cell line (HCT116GH) from parental diploid colorectal cancer cell line (HCT116) via PEG-mediated cell fusion and compared its cell viability, cell cycle response and apoptotic fractions responded to H2O2 with diploid HCT116 and p53 suppressed HCT116/H6 cell lines. RESULTS: Using MTT assay, plating efficiency and clonogenicity, we evaluated the survival of each cell line. Tetraploid cell line HCT116GH demonstrated an 83 fold greater resistance to 100 microM H2O2 than the parental diploid HCT116, and 6 fold greater than even the p53 negative diploid HCT116/E6. Cellular sensitivity, G2/M arrests, and apoptotic proportion were observed less in response to H2O2 in HCT116GH compared with HCT116 and HCT116/E6. HCT116GH expressed lower level of p53 and p21 than diploid HCT116. CONCLUSIONS: Stable tetraploid cell lines showed enhanced viability in comparison to parental diploid cell lines. The enhanced viability observed in tetraploidization surpassed that from downregulation of p53. Frequent appearance of tetraploid cells in stressful condition can be caused by natural selection owing to their enhanced viability and may consequently contribute to cancer cell transformation.
