Step-wise and punctuated genome evolution drive phenotype changes of tumor cells

HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution

“…293 cells at our disposal (a gift from the Department of Structural and Molecular Biology, University College London, UK) had the chromosome number mainly 63-78, with more than 40% of cells having 72-76 chromosomes/cell (Stepanenko et al, 2015). Importantly, the majority of chromosome aberrations, which we have detected in 293 cells (Stepanenko et al, 2015), were distinct from those reported by Bylund et al (2004) and partially similar to those listed by ATCC. Thus, the mean chromosome number and chromosome aberrations are significantly distinct in 293 cells from the different sources arguing that the long-term cultivated and propagated clones of 293 cells could undergo significant karyotype changes and selection.…”

“…Importantly, genome instability caused by a stable empty vector transfection (or long-term drug treatment) correlated with the growth characteristic changes of 293 cells (e.g., survival and colony formation efficiency in soft agar) (Stepanenko et al, 2015). Consistent evolution of karyotypes and phenotypes in different models was shown Duesberg et al, 2007Duesberg et al, , 2011Duesberg et al, , 2012Klein et al, 2010;Li et al, 2009;McCormack et al, 2013;Nicholson and Duesberg, 2009).…”

“…Another piece of evidence of the genome dynamics of 293 cells in response to the common experimental manipulations comes from our recent study, where we have reported that a stable transfection of the empty vector pcDNA3.1 into 293 cells promoted CIN (clonal and nonclonal chromosome aberrations) and increased genomic heterogeneity (Stepanenko et al, 2015). Previously, Bylund et al revealed that the empty vector transfected 293_pVgRXR cells (named EcR-293 from Invitrogen) had less total chromosome number (hyperdiploid) but higher number of aberrant chromosomes, and only one derivative chromosome was common with the wild type hypotriploid 293 cells from ECACC (Salisbury, UK).…”

“…The mean chromosome number of 293 cells from LGC Prochem AB (Bucas, Sweden) was 56.7 (Stavropoulou et al, 2005). 293 cells at our disposal (a gift from the Department of Structural and Molecular Biology, University College London, UK) had the chromosome number mainly 63-78, with more than 40% of cells having 72-76 chromosomes/cell (Stepanenko et al, 2015). Importantly, the majority of chromosome aberrations, which we have detected in 293 cells (Stepanenko et al, 2015), were distinct from those reported by Bylund et al (2004) and partially similar to those listed by ATCC.…”

“…293 cells constitutively express Ad5 E1A/E1B proteins (Komorek et al, 2010) with similar functions on deregulation of pRB/p53 pathways (Stepanenko and Kavsan, 2012). Many CNAs with a significant overlap with CFSs were revealed in 293 cells (Lin et al, 2014;Stepanenko et al, 2015). In general, acute stress such as modulation of expression/activity of cancer-associated genes is capable of inducing replication stress, DNA double strand breaks, and DNA damage response (Corcos, 2012;Dereli-Öz et al, 2011;Mortusewicz et al, 2013;Neelsen et al, 2013).…”