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

Nugoli, Mélanie; Chuchana, Paul; Vendrell, Julie A.; Orsetti, Béatrice; Ursule, Lisa; Nguyen, Catherine; Birnbaum, Daniel; Douzery, Emmanuel J. P.; Cohen, Pascale A.; Theillet, Charles

doi:10.1186/1471-2407-3-13

Cited by 84 publications

(81 citation statements)

References 30 publications

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“…Notably, normal breast-derived cell lines MCF-10A and 184B5, and Hs578T and MDA-MB-231 expressed mostly basal and mesenchymal/stromal genes, respectively (Ross and Perou, 2001 Foulkes et al, 2004). The results further suggest that molecular subtypes represent prominent biological processes overcoming possible variations in gene expression in cell lines grown in different settings (Nugoli et al, 2003). We and others (Sorlie et al, 2001;Bertucci et al, 2004a) have found that ERBB2 tumours merged more with ERÀ tumours expressing strong basal/myoepithelial-like and normal-like signature than with luminal ER þ samples.…”

Section: Expression Profiling Of Breast Cell Lines E Charafe-jauffretmentioning

confidence: 64%

Gene expression profiling of breast cell lines identifies potential new basal markers

et al. 2005

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International audienceA better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression pro. ling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on `cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published `intrinsic 500-gene set' assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management

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Section: Expression Profiling Of Breast Cell Lines E Charafe-jauffretmentioning

confidence: 64%

Gene expression profiling of breast cell lines identifies potential new basal markers

et al. 2005

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“…are the same cell line [20]. Indeed, our stocks had identical STR profiles, shared the E545 K PIK3CA mutation ( Table-S1) and had very similar transcriptional profiles ( Fig.…”

Section: Short Tandem Repeat (Str)-profiling and Targeted Mutation Anmentioning

confidence: 90%

Multidimensional phenotyping of breast cancer cell lines to guide preclinical research

Saunus

Smart

Kutasovic

et al. 2017

Breast Cancer Res Treat

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Purpose Cell lines are extremely useful tools in breast cancer research. Their key benefits include a high degree of control over experimental variables and reproducibility. However, the advantages must be balanced against the limitations of modelling such a complex disease in vitro. Informed selection of cell line(s) for a given experiment now requires essential knowledge about molecular and phenotypic context in the culture dish.

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“…We first defined threshold exposure conditions for an HSP90 inhibitor that alone would exert no direct effect on growth of the ER+ breast cancer cell line MCF-7. This line was established from the pleural effusion of a patient with metastatic disease and displays considerable clonal heterogeneity at the genetic and phenotypic levels (23). As the HSP90 inhibitor, we chose ganetespib, a synthetic second-generation agent in late-stage clinical development that has markedly improved pharmacology over earlier natural product-derived compounds (24,25).…”

Section: Resultsmentioning

confidence: 99%

HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models

Whitesell

Santagata

Mendillo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

105

107

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The efficacy of hormonal therapies for advanced estrogen receptorpositive breast cancers is limited by the nearly inevitable development of acquired resistance. Efforts to block the emergence of resistance have met with limited success, largely because the mechanisms underlying it are so varied and complex. Here, we investigate a new strategy aimed at the very processes by which cancers evolve resistance. From yeast to vertebrates, heat shock protein 90 (HSP90) plays a unique role among molecular chaperones by promoting the evolution of heritable new traits. It does so by regulating the folding of a diverse portfolio of metastable client proteins, many of which mediate adaptive responses that allow organisms to adapt and thrive in the face of diverse challenges, including those posed by drugs. Guided by our previous work in pathogenic fungi, in which very modest HSP90 inhibition impairs resistance to mechanistically diverse antifungals, we examined the effect of similarly modest HSP90 inhibition on the emergence of resistance to antiestrogens in breast cancer models. Even though this degree of inhibition fell below the threshold for proteotoxic activation of the heat-shock response and had no overt anticancer activity on its own, it dramatically impaired the emergence of resistance to hormone antagonists both in cell culture and in mice. Our findings strongly support the clinical testing of combined hormone antagonist-low-level HSP90 inhibitor regimens in the treatment of metastatic estrogen receptor-positive breast cancer. At a broader level, they also provide promising proof of principle for a generalizable strategy to combat the pervasive problem of rapidly emerging resistance to molecularly targeted therapeutics.estrogen receptor | antiestrogen | drug resistance | tumor progression | tamoxifen D rastically limiting the efficacy of targeted therapeutics, the emergence of drug resistance in advanced cancers remains nearly inevitable. From yeast to vertebrates, the molecular chaperone heat shock protein 90 (HSP90) allows organisms to adapt and thrive in the face of diverse challenges, including those posed by drugs and environmental stressors (1, 2). It does so by regulating the folding of a highly diverse portfolio of metastable client proteins, many mediating adaptive responses (3, 4).However, this role for HSP90 in adaptation is greatly magnified by its ability to promote the evolution of heritable new traits. To buffer the proteome against unexpected environmental challenges, HSP90 is present in large excess under normal circumstances. This buffering capacity allows it to modulate the manifestation of preexisting and newly acquired genetic variation within heterogeneous populations of cells, and even whole organisms, thereby dramatically expanding the range of phenotypes on which selection can act (1, 2, 5-7). As a dramatic, therapeutically relevant example, we have shown that this HSP90 buffer enables fungal pathogens spanning ∼1 billion years of evolution to evolve and maintain resistance to every major a...

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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.

Cited by 84 publications

References 30 publications

Gene expression profiling of breast cell lines identifies potential new basal markers

Gene expression profiling of breast cell lines identifies potential new basal markers

Multidimensional phenotyping of breast cancer cell lines to guide preclinical research

HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models

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