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Differential expression of centrosome regulators in Her2+ breast cancer cells versus non-tumorigenic MCF10A cells

Overview of attention for article published in Cell Division, September 2014
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Title
Differential expression of centrosome regulators in Her2+ breast cancer cells versus non-tumorigenic MCF10A cells
Published in
Cell Division, September 2014
DOI 10.1186/1747-1028-9-3
Pubmed ID
Authors

Mi-Young Lee, Mihaela Marina, Jamie L King, Harold I Saavedra

Abstract

Centrosome amplification (CA) amongst particular breast cancer subtypes (Her2+ subtype) is associated with genomic instability and aggressive tumor phenotypes. However, changes in signaling pathways associated with centrosome biology have not been fully explored in subtype specific models. Novel centrosome regulatory genes that are selectively altered in Her2+ breast cancer cells are of interest in discerning why CA is more prevalent in this subtype. To determine centrosome/cell cycle genes that are altered in Her2+ cells that display CA (HCC1954) versus non-tumorigenic cells (MCF10A), we carried out a gene microarray. Expression differences were validated by real-time PCR and Western blotting. After the microarray validation, we pursued a panel of upregulated and downregulated genes based on novelty/relevance to centrosome duplication. Functional experiments measuring CA and BrdU incorporation were completed after genetic manipulation of targets (TTK, SGOL1, MDM2 and SFRP1). Amongst genes that were downregulated in HCC1954 cells, knockdown of MDM2 and SFRP1 in MCF10A cells did not consistently induce CA or impaired BrdU incorporation. Conversely, amongst upregulated genes in HCC1954 cells, knockdown of SGOL1 and TTK decreased CA in breast cancer cells, while BrdU incorporation was only altered by SGOL1 knockdown. We also explored the Kaplan Meier Plot resource and noted that MDM2 and SFRP1 are positively associated with relapse free survival in all breast cancer subtypes, while TTK is negatively correlated with overall survival of Luminal A patients. Based on this functional screen, we conclude that SGOL1 and TTK are important modulators of centrosome function in a breast cancer specific model.

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Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 1 6%
Unknown 16 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 29%
Researcher 3 18%
Student > Master 3 18%
Lecturer 1 6%
Professor 1 6%
Other 2 12%
Unknown 2 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 35%
Agricultural and Biological Sciences 6 35%
Pharmacology, Toxicology and Pharmaceutical Science 2 12%
Medicine and Dentistry 1 6%
Unknown 2 12%