The prognostic significance of Cdc6 and Cdt1 in breast cancer
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 stu...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-04-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-00998-9 |
| _version_ | 1829464564170752000 |
|---|---|
| author | Ravikiran Mahadevappa Henrique Neves Shun Ming Yuen Yuchen Bai Cian M. McCrudden Hiu Fung Yuen Qing Wen Shu Dong Zhang Hang Fai Kwok |
| author_facet | Ravikiran Mahadevappa Henrique Neves Shun Ming Yuen Yuchen Bai Cian M. McCrudden Hiu Fung Yuen Qing Wen Shu Dong Zhang Hang Fai Kwok |
| author_sort | Ravikiran Mahadevappa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T16:39:27Z |
| format | Article |
| id | doaj.art-5d67ca260d2d4a3ba651bf96ea3d89ef |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:39:27Z |
| publishDate | 2017-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5d67ca260d2d4a3ba651bf96ea3d89ef2022-12-21T23:38:19ZengNature PortfolioScientific Reports2045-23222017-04-017111110.1038/s41598-017-00998-9The prognostic significance of Cdc6 and Cdt1 in breast cancerRavikiran Mahadevappa0Henrique Neves1Shun Ming Yuen2Yuchen Bai3Cian M. McCrudden4Hiu Fung Yuen5Qing Wen6Shu Dong Zhang7Hang Fai Kwok8Faculty of Health Sciences, University of Macau, Avenida de UniversidadeFaculty of Health Sciences, University of Macau, Avenida de UniversidadeFaculty of Health Sciences, University of Macau, Avenida de UniversidadeFaculty of Health Sciences, University of Macau, Avenida de UniversidadeSchool of Pharmacy, Queen’s University BelfastInstitute of Molecular and Cell Biology, A*STARCentre for Cancer Research & Cell Biology and Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University BelfastNorthern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster UniversityFaculty of Health Sciences, University of Macau, Avenida de UniversidadeAbstract 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.https://doi.org/10.1038/s41598-017-00998-9 |
| spellingShingle | Ravikiran Mahadevappa Henrique Neves Shun Ming Yuen Yuchen Bai Cian M. McCrudden Hiu Fung Yuen Qing Wen Shu Dong Zhang Hang Fai Kwok The prognostic significance of Cdc6 and Cdt1 in breast cancer Scientific Reports |
| title | The prognostic significance of Cdc6 and Cdt1 in breast cancer |
| title_full | The prognostic significance of Cdc6 and Cdt1 in breast cancer |
| title_fullStr | The prognostic significance of Cdc6 and Cdt1 in breast cancer |
| title_full_unstemmed | The prognostic significance of Cdc6 and Cdt1 in breast cancer |
| title_short | The prognostic significance of Cdc6 and Cdt1 in breast cancer |
| title_sort | prognostic significance of cdc6 and cdt1 in breast cancer |
| url | https://doi.org/10.1038/s41598-017-00998-9 |
| work_keys_str_mv | AT ravikiranmahadevappa theprognosticsignificanceofcdc6andcdt1inbreastcancer AT henriqueneves theprognosticsignificanceofcdc6andcdt1inbreastcancer AT shunmingyuen theprognosticsignificanceofcdc6andcdt1inbreastcancer AT yuchenbai theprognosticsignificanceofcdc6andcdt1inbreastcancer AT cianmmccrudden theprognosticsignificanceofcdc6andcdt1inbreastcancer AT hiufungyuen theprognosticsignificanceofcdc6andcdt1inbreastcancer AT qingwen theprognosticsignificanceofcdc6andcdt1inbreastcancer AT shudongzhang theprognosticsignificanceofcdc6andcdt1inbreastcancer AT hangfaikwok theprognosticsignificanceofcdc6andcdt1inbreastcancer AT ravikiranmahadevappa prognosticsignificanceofcdc6andcdt1inbreastcancer AT henriqueneves prognosticsignificanceofcdc6andcdt1inbreastcancer AT shunmingyuen prognosticsignificanceofcdc6andcdt1inbreastcancer AT yuchenbai prognosticsignificanceofcdc6andcdt1inbreastcancer AT cianmmccrudden prognosticsignificanceofcdc6andcdt1inbreastcancer AT hiufungyuen prognosticsignificanceofcdc6andcdt1inbreastcancer AT qingwen prognosticsignificanceofcdc6andcdt1inbreastcancer AT shudongzhang prognosticsignificanceofcdc6andcdt1inbreastcancer AT hangfaikwok prognosticsignificanceofcdc6andcdt1inbreastcancer |