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

Abstract : BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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https://www.hal.inserm.fr/inserm-00115589
Contributor : Yves Le Ster <>
Submitted on : Thursday, November 30, 2006 - 4:10:55 PM
Last modification on : Wednesday, October 14, 2020 - 3:50:13 AM
Long-term archiving on: : Thursday, September 20, 2012 - 2:56:35 PM

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Mélanie Nugoli, Paul Chuchana, Julie Vendrell, Béatrice Orsetti, Lisa Ursule, et al.. Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications.. BMC Cancer, BioMed Central, 2003, 3, pp.13. ⟨10.1186/1471-2407-3-13⟩. ⟨inserm-00115589⟩

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