Genetic variability in MCF-7 sublines: Evidence of rapid genomic and RNA expression profile modifications

Equipe Génome et Cancer, UMR 5535, CNRS and EMI 0229, INSERM, Centre de Recherche CRLC Val d'Aurelle, Montpellier, France.
BMC Cancer (Impact Factor: 3.36). 05/2003; 3:13. DOI: 10.1186/1471-2407-3-13
Source: PubMed


Both phenotypic and cytogenetic variability have been reported for clones of breast carcinoma cell lines but have not been comprehensively studied. Despite this, cell lines such as MCF-7 cells are extensively used as model systems.
In this work we documented, using CGH and RNA expression profiles, the genetic variability at the genomic and RNA expression levels of MCF-7 cells of different origins. Eight MCF-7 sublines collected from different sources were studied as well as 3 subclones isolated from one of the sublines by limit dilution.
MCF-7 sublines showed important differences in copy number alteration (CNA) profiles. Overall numbers of events ranged from 28 to 41. Involved chromosomal regions varied greatly from a subline to another. A total of 62 chromosomal regions were affected by either gains or losses in the 11 sublines studied. We performed a phylogenetic analysis of CGH profiles using maximum parsimony in order to reconstruct the putative filiation of the 11 MCF-7 sublines. The phylogenetic tree obtained showed that the MCF-7 clade was characterized by a restricted set of 8 CNAs and that the most divergent subline occupied the position closest to the common ancestor. Expression profiles of 8 MCF-7 sublines were analyzed along with those of 19 unrelated breast cancer cell lines using home made cDNA arrays comprising 720 genes. Hierarchical clustering analysis of the expression data showed that 7/8 MCF-7 sublines were grouped forming a cluster while the remaining subline clustered with unrelated breast cancer cell lines. These data thus showed that MCF-7 sublines differed at both the genomic and phenotypic levels.
The analysis of CGH profiles of the parent subline and its three subclones supported the heteroclonal nature of MCF-7 cells. This strongly suggested that the genetic plasticity of MCF-7 cells was related to their intrinsic capacity to generate clonal heterogeneity. We propose that MCF-7, and possibly the breast tumor it was derived from, evolved in a node like pattern, rather than according to a linear progression model. Due to their capacity to undergo rapid genetic changes MCF-7 cells could represent an interesting model for genetic evolution of breast tumors.

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    • "MCF-7, a commonly used breast cancer cell line, has been propagated for many years by multiple groups and it might be expected that such propagation would select a single phenotype that had the highest growth rate. However, the finding of extensive heterogeneity among MCF-7 lines used by different groups (Nugoli et al., 2003) suggests that mechanisms may be operating within proliferating MCF-7 populations to generate phenotypic diversity continuously. The aim of this chapter is to discuss the evidence of the way that the MCF-7 breast cancer cell line is heterogeneous with respect to both the expression of hormone receptors and to the utilization of the signalling pathways linked to these receptors. "

    Breast Cancer - Carcinogenesis, Cell Growth and Signalling Pathways, 11/2011; , ISBN: 978-953-307-714-7
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    • "This is accentuated by the fact that sub-lines derived from the same tumour may exhibit distinct genomic profiles. Detailed analyses of different sub-lines from the commonly used MCF-7 breast cancer cell line have shown that there is wide genetic variation among the different lines with respect to genomic imbalances and expression profiles [12]. This considered, surprisingly little is known about the principles guiding in vitro genetic evolution of established cancer cell lines after the first phase of clonal selection at cell line establishment. "
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    • "While the BFB may account for the steep slope of rise in genomic complexity in MCF-7 during the stage of in situ carcinoma and telomere crisis, the subsequent instability mediated by the failure of the homologybased DSB repair mechanism resulting in breaks at LCR loci may account for the subsequent less steep slope that typically follows completion of the telomere crisis stage and accompanies metastasis. The two-stage model is also consistent with ongoing plasticity of the MCF-7 genome as evidenced by polyclonality and divergence of MCF-7 sublines (Jones et al. 2000; Nugoli et al. 2003). "
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