Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer.
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Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer. / Choschzick, Matthias; Lebeau, Annette; Marx, Andreas; Tharun, Lars; Terracciano, Luigi; Heilenkötter, Uwe; Jänicke, Fritz; Bokemeyer, Carsten; Simon, Ronald; Sauter, Guido; Schwarz, Jörg.
in: HUM PATHOL, 2009.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer.
AU - Choschzick, Matthias
AU - Lebeau, Annette
AU - Marx, Andreas
AU - Tharun, Lars
AU - Terracciano, Luigi
AU - Heilenkötter, Uwe
AU - Jänicke, Fritz
AU - Bokemeyer, Carsten
AU - Simon, Ronald
AU - Sauter, Guido
AU - Schwarz, Jörg
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
JO - HUM PATHOL
JF - HUM PATHOL
SN - 0046-8177
ER -