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Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer

Choschzick, Matthias and Lebeau, Annette and Marx, Andreas H. and Tharun, Lars and Terracciano, Luigi and Heilenkötter, Uwe and Jaenicke, Fritz and Bokemeyer, Carsten and Simon, Ronald and Sauter, Guido and Schwarz, Jörg. (2010) Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer. Human pathology, Vol. 41, H. 3. pp. 358-365.

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Official URL: http://edoc.unibas.ch/dok/A6006154

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Abstract

Cell division cycle 7 is a widely expressed protein kinase implicated in cell division, cell cycle checkpoint mechanisms, and cancer progression. To determine the relationship of cell division cycle 7 protein expression with tumor phenotype, molecular features and prognosis, 2197 highly characterized breast carcinomas were analyzed on a tissue microarray. Detectable cell division cycle 7 expression was found in 1088 (57%) of breast cancer specimens and 228 (11.9%) exhibited a moderate or strong expression. High levels of cell division cycle 7 expression were significantly related to medullary histotype (P > .0001); high tumor grade (P > .0001); negative estrogen receptor status (P > .0001); high Ki67 expression level (P > .0001); p53 and p16 overexpression (P > .0001); and amplification of HER2 (P > .0001), c-myc (P > .0001), MDM2 (P = .043), CCND1 (P = .0084), and ESR1 (P = .0012) as well as with the number of amplified genes (P > .0001). There was also a tendency towards worse prognosis in cell division cycle 7 positive as compared to negative breast cancers. The relationship between cell division cycle 7 and number of amplifications was independent from tumor proliferation raising the possibility of a direct influence of cell division cycle 7 expression for amplification development. In conclusion, cell division cycle 7 is a replication associated protein with relationships to gene amplification and genomic instability in breast carcinomas. These data support the potential utility of newly developed small molecule cell division cycle 7 inhibitors as a therapeutic alternative in at least a subset of breast carcinomas.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
UniBasel Contributors:Terracciano, Luigi M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:W.B. Saunders
ISSN:0046-8177
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Jun 2013 12:29
Deposited On:21 Jun 2013 12:24

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