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Dysregulation of Gene Expression in the Artificial Human Trisomy Cells of Chromosome 8 Associated with Transformed Cell Phenotypes

By Hisakatsu Nawata, Genro Kashino, Keizo Tano, Kazuhiro Daino, Yoshiya Shimada, Hiroyuki Kugoh, Mitsuo Oshimura and Masami Watanabe

Abstract

A change in chromosome number, known as aneuploidy, is a common characteristic of cancer. Aneuploidy disrupts gene expression in human cancer cells and immortalized human epithelial cells, but not in normal human cells. However, the relationship between aneuploidy and cancer remains unclear. To study the effects of aneuploidy in normal human cells, we generated artificial cells of human primary fibroblast having three chromosome 8 (trisomy 8 cells) by using microcell-mediated chromosome transfer technique. In addition to decreased proliferation, the trisomy 8 cells lost contact inhibition and reproliferated after exhibiting senescence-like characteristics that are typical of transformed cells. Furthermore, the trisomy 8 cells exhibited chromosome instability, and the overall gene expression profile based on microarray analyses was significantly different from that of diploid human primary fibroblasts. Our data suggest that aneuploidy, even a single chromosome gain, can be introduced into normal human cells and causes, in some cases, a partial cancer phenotype due to a disruption in overall gene expression

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3183047
Provided by: PubMed Central

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Citations

  1. (1991). A
  2. (1997). A clinical overview of WT1 gene mutations.
  3. (2007). Aberrant DNA methylation of the 59 upstream region of Tslc1 gene in hamster pancreatic tumors.
  4. (2008). Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells.
  5. (2007). Cell biology: Chromosome territories.
  6. (1996). Cell Contact-Dependent Signaling.
  7. (2007). Chromosomal Aberrations and Cancer Risk: Results of a Cohort Study from Central Europe.
  8. (1995). Chromosome aberrations in desmoid tumors trisomy 8 may be a predictor of recurrence.
  9. (2004). Chromosome transfer induced aneuploidy results in complex dysregulation of the cellular transcriptome in immortalized and cancer cells.
  10. (1993). Consistent numerical chromosome aberrations in congenital fibrosarcoma.
  11. (2009). Constitutional aneuploidy and cancer predisposition.
  12. (2001). Culture condition-dependent senescence-like growth arrest and immortalization in rodent embryo cells.
  13. (2005). DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis.
  14. (2002). DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1.
  15. (2006). Does aneuploidy cause cancer?
  16. (2007). Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions.
  17. (2005). Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas.
  18. (2001). Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics.
  19. (1998). Extension of in vitro life-span of gamma-irradiated human embryo cells accompanied by chromosome instability.
  20. (1994). Fibrosarcoma in Infants and Children: Application of New Techniques.
  21. Halazonetis TD (2000) p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA doublestrand breaks.
  22. (2000). Hayflick, his limit, and cellular ageing.
  23. (2007). hepatocellular carcinomas induced by N-nitrosodiethylamine in rats.
  24. (1990). Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping.
  25. (1995). Homozygous intragenic deletion in the WT1 gene in a sporadic Wilms’ tumour associated with high levels of expression of a truncated transcript.
  26. (1981). Humantumor-derived cell lines contain common and different transforming genes.
  27. (2005). Involvement of a cell adhesion molecule, TSLC1/IGSF4, in human oncogenesis.
  28. (1990). Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus.
  29. (2005). Loss of TSLC1 expression in lung adenocarcinoma: Relationships with histological subtypes, sex and prognostic significance.
  30. (2003). Microcell-mediated chromosome transfer (MMCT): small cells with huge potential.
  31. (1999). Mouse A9 cells containing single human chromosomes for analysis of genomic imprinting.
  32. (2007). Nuclear organization of the genome and the potential for gene regulation.
  33. (2003). Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines.
  34. (2004). Re-expression of TSLC1 in a non-small-cell lung cancer cell line induces apoptosis and inhibits tumor growth.
  35. (1998). Telomerase activity, telomere length, and chromosome aberrations in the extension of life span of human embryo cells induced by low-dose X-rays.
  36. (2000). The in vitro micronucleus technique.
  37. (2002). The Role of WT1 in Oncogenesis: Tumor Suppressor or Oncogene?
  38. (1993). The role of WT1 in Wilms tumorigenesis.
  39. (1961). The serial cultivation of human diploid cell strains.
  40. (1993). The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor.
  41. (2001). To err (meiotically) is human: the genesis of human aneuploidy.
  42. (2001). TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer.
  43. (2009). Tumor suppressor CADM1 is involved in epithelial cell structure.
  44. (2001). Tumor Suppressor P53 Binding Protein 1 (53bp1) Is Involved in DNA Damage–Signaling Pathways.
  45. (2002). Visualizing Chromatin Dynamics in Interphase Nuclei.
  46. (2011). Wilms’ tumours: about tumour suppressor genes, an oncogene and a chameleon gene.
  47. (2010). WT1 (Wilms’ tumor gene 1): biology and cancer immunotherapy.
  48. (1993). WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.