Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications
<p>Abstract</p> <p>Background</p> <p>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.&l...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2003-04-01
|
| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/3/13 |
| _version_ | 1819180442602962944 |
|---|---|
| author | Douzery Emmanuel JP Birnbaum Daniel Nguyen Catherine Ursule Lisa Orsetti Béatrice Vendrell Julie Chuchana Paul Nugoli Mélanie Cohen Pascale Theillet Charles |
| author_facet | Douzery Emmanuel JP Birnbaum Daniel Nguyen Catherine Ursule Lisa Orsetti Béatrice Vendrell Julie Chuchana Paul Nugoli Mélanie Cohen Pascale Theillet Charles |
| author_sort | Douzery Emmanuel JP |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-22T22:14:25Z |
| format | Article |
| id | doaj.art-b1643cdfb30a4209a068dedffcb6d529 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-22T22:14:25Z |
| publishDate | 2003-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-b1643cdfb30a4209a068dedffcb6d5292022-12-21T18:10:49ZengBMCBMC Cancer1471-24072003-04-01311310.1186/1471-2407-3-13Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modificationsDouzery Emmanuel JPBirnbaum DanielNguyen CatherineUrsule LisaOrsetti BéatriceVendrell JulieChuchana PaulNugoli MélanieCohen PascaleTheillet Charles<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2407/3/13 |
| spellingShingle | Douzery Emmanuel JP Birnbaum Daniel Nguyen Catherine Ursule Lisa Orsetti Béatrice Vendrell Julie Chuchana Paul Nugoli Mélanie Cohen Pascale Theillet Charles Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications BMC Cancer |
| title | Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications |
| title_full | Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications |
| title_fullStr | Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications |
| title_full_unstemmed | Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications |
| title_short | Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications |
| title_sort | genetic variability in mcf 7 sublines evidence of rapid genomic and rna expression profile modifications |
| url | http://www.biomedcentral.com/1471-2407/3/13 |
| work_keys_str_mv | AT douzeryemmanueljp geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT birnbaumdaniel geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT nguyencatherine geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT ursulelisa geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT orsettibeatrice geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT vendrelljulie geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT chuchanapaul geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT nugolimelanie geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT cohenpascale geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications AT theilletcharles geneticvariabilityinmcf7sublinesevidenceofrapidgenomicandrnaexpressionprofilemodifications |