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

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.

Dosage compensation and inverse effects in triple X metafemales of Drosophila

“…Studies of gene expression in yeasts and mammals in disomics or trisomics have reported differing results as to compensation and trans-effects (e.g., refs. [35][36][37][38] vs. claims of primarily dosage effects of the varied genes (e.g., refs. 39, 40).…”

The deregulated microRNAome contributes to the cellular response to aneuploidy

“…Recently developed aneuploid model systems in several different species have accelerated research on the effects of aneuploidy per se. The physiological changes in response to an unbalanced karyotype are multifold, including impaired proliferation, replication stress and proteotoxic stress that is characterized by changes in protein stoichiometry, reduced protein folding capacity and by activation of autophagy [4][5][6][7][8][9][10][11][12][13]. The physiological response to aneuploidy goes hand in hand with a transcriptional response that is manifested in a conserved pathway deregulation [14,15].…”

Gene balance hypothesis: Connecting issues of dosage sensitivity across biological disciplines

“…This effect is quite common in the data for trisomic segments in other species. including Datura, barley, Arabidopsis, Drosophila, and human trisomic cells (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). The ability to recover corresponding monosomics in maize facilitated the finding that this effect can be proportional through one, two, and three doses.…”