The prognostic significance of Cdc6 and Cdt1 in breast cancer

Ravikiran Mahadevappa, Henrique Neves, Shun Ming Yuen, Yuchen Bai, Cian M. McCrudden, Hiu Fung Yuen, Qing Wen, Shu-Dong Zhang, Hang Fai Kwok

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18 Citations (Scopus)

Abstract

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.
Original languageEnglish
Article number985
JournalScientific Reports
Volume7
Issue number1
Early online date20 Apr 2017
DOIs
Publication statusE-pub ahead of print - 20 Apr 2017

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Keywords

  • Cdc6
  • Cdt1
  • breast cancer

Cite this

Mahadevappa, R., Neves, H., Yuen, S. M., Bai, Y., McCrudden, C. M., Yuen, H. F., ... Kwok, H. F. (2017). The prognostic significance of Cdc6 and Cdt1 in breast cancer. Scientific Reports, 7(1), [985]. https://doi.org/10.1038/s41598-017-00998-9