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The prognostic significance of Cdc6 and Cdt1 in breast cancer
Mahadevappa, Ravikiran1; Neves, Henrique1; Yuen, Shun Ming1; Bai, Yuchen1; McCrudden, Cian M.2; Yuen, Hiu Fung3; Wen, Qing4; Zhang, Shu Dong5; Kwok, Hang Fai1

DNA replication is a critical step in cell proliferation. Overexpression of MCM2-7 genes correlated with poor prognosis in breast cancer patients. However, the roles of Cdc6 and Cdt1, which work with MCMs to regulate DNA replication, in breast cancers are largely unknown. In the present study, we have shown that the expression levels of Cdc6 and Cdt1 were both significantly correlated with an increasing number of MCM2-7 genes overexpression. Both Cdc6 and Cdt1, when expressed in a high level, alone or in combination, were significantly associated with poorer survival in the breast cancer patient cohort (n = 1441). In line with this finding, the expression of Cdc6 and Cdt1 was upregulated in breast cancer cells compared to normal breast epithelial cells. Expression of Cdc6 and Cdt1 was significantly higher in ER negative breast cancer, and was suppressed when ER signalling was inhibited either by tamoxifen in vitro or letrozole in human subjects. Importantly, breast cancer patients who responded to letrozole expressed significantly lower Cdc6 than those patients who did not respond. Our results suggest that Cdc6 is a potential prognostic marker and therapeutic target in breast cancer patients.

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Indexed BySCI
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000399693500003
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Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR, China
2.School of Pharmacy, Queen’s University Belfast, Belfast, UK
3.Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore
4.Centre for Cancer Research & Cell Biology and Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK
5.Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry, UK
First Author AffilicationFaculty of Health Sciences
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GB/T 7714
Mahadevappa, Ravikiran,Neves, Henrique,Yuen, Shun Ming,et al. The prognostic significance of Cdc6 and Cdt1 in breast cancer[J]. SCIENTIFIC REPORTS,2017,7.
APA Mahadevappa, Ravikiran.,Neves, Henrique.,Yuen, Shun Ming.,Bai, Yuchen.,McCrudden, Cian M..,...&Kwok, Hang Fai.(2017).The prognostic significance of Cdc6 and Cdt1 in breast cancer.SCIENTIFIC REPORTS,7.
MLA Mahadevappa, Ravikiran,et al."The prognostic significance of Cdc6 and Cdt1 in breast cancer".SCIENTIFIC REPORTS 7(2017).
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