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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-04-24

AUTHORS

Mélanie Nugoli, Paul Chuchana, Julie Vendrell, Béatrice Orsetti, Lisa Ursule, Catherine Nguyen, Daniel Birnbaum, Emmanuel JP Douzery, Pascale Cohen, Charles Theillet

ABSTRACT

BackgroundBoth 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.MethodsIn 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.ResultsMCF-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.ConclusionsThe 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. More... »

PAGES

13

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2407-3-13

DOI

http://dx.doi.org/10.1186/1471-2407-3-13

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1037728403

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12713671


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68 expression data
69 expression levels
70 expression profiles
71 filiation
72 gain
73 genes
74 genetic evolution
75 genetic plasticity
76 genetic variability
77 genomics
78 heterogeneity
79 home
80 important differences
81 interesting model
82 intrinsic capacity
83 levels
84 limit dilution
85 linear progression model
86 lines
87 loss
88 maximum parsimony
89 model
90 model system
91 modification
92 nature
93 nodes
94 number
95 number alteration profiles
96 order
97 origin
98 overall number
99 parsimony
100 patterns
101 phenotypic
102 phenotypic level
103 phylogenetic analysis
104 phylogenetic tree
105 plasticity
106 position
107 profile
108 profile modification
109 progression model
110 rapid genomic
111 region
112 set
113 source
114 subclones
115 sublines
116 system
117 total
118 trees
119 tumors
120 variability
121 work
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