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Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressi...

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Autores principales: Zhao, Xiangshan, Mirza, Sameer, Alshareeda, Alaa, Zhang, Ying, Gurumurthy, Channabasavaiah Basavaraju, Bele, Aditya, Kim, Jun Hyun, Mohibi, Shakur, Goswami, Monica, Lele, Subodh M., West, William, Qiu, Fang, Ellis, Ian O., Rakha, Emad A., Green, Andrew R., Band, Hamid, Band, Vimla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397230/
https://www.ncbi.nlm.nih.gov/pubmed/22270930
http://dx.doi.org/10.1007/s10549-011-1946-8
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author Zhao, Xiangshan
Mirza, Sameer
Alshareeda, Alaa
Zhang, Ying
Gurumurthy, Channabasavaiah Basavaraju
Bele, Aditya
Kim, Jun Hyun
Mohibi, Shakur
Goswami, Monica
Lele, Subodh M.
West, William
Qiu, Fang
Ellis, Ian O.
Rakha, Emad A.
Green, Andrew R.
Band, Hamid
Band, Vimla
author_facet Zhao, Xiangshan
Mirza, Sameer
Alshareeda, Alaa
Zhang, Ying
Gurumurthy, Channabasavaiah Basavaraju
Bele, Aditya
Kim, Jun Hyun
Mohibi, Shakur
Goswami, Monica
Lele, Subodh M.
West, William
Qiu, Fang
Ellis, Ian O.
Rakha, Emad A.
Green, Andrew R.
Band, Hamid
Band, Vimla
author_sort Zhao, Xiangshan
collection PubMed
description Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P = 0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P = 0.013), mitotic index (P = 0.032), and Nottingham Prognostic Index score (P = 0.014). Ecd expression was positively associated with HER2/neu (P = 0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P = 0.008) and disease-free survival (DFS) (P = 0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-011-1946-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-33972302012-07-23 Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients Zhao, Xiangshan Mirza, Sameer Alshareeda, Alaa Zhang, Ying Gurumurthy, Channabasavaiah Basavaraju Bele, Aditya Kim, Jun Hyun Mohibi, Shakur Goswami, Monica Lele, Subodh M. West, William Qiu, Fang Ellis, Ian O. Rakha, Emad A. Green, Andrew R. Band, Hamid Band, Vimla Breast Cancer Res Treat Preclinical Study Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P = 0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P = 0.013), mitotic index (P = 0.032), and Nottingham Prognostic Index score (P = 0.014). Ecd expression was positively associated with HER2/neu (P = 0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P = 0.008) and disease-free survival (DFS) (P = 0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-011-1946-8) contains supplementary material, which is available to authorized users. Springer US 2012-01-22 2012 /pmc/articles/PMC3397230/ /pubmed/22270930 http://dx.doi.org/10.1007/s10549-011-1946-8 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Preclinical Study
Zhao, Xiangshan
Mirza, Sameer
Alshareeda, Alaa
Zhang, Ying
Gurumurthy, Channabasavaiah Basavaraju
Bele, Aditya
Kim, Jun Hyun
Mohibi, Shakur
Goswami, Monica
Lele, Subodh M.
West, William
Qiu, Fang
Ellis, Ian O.
Rakha, Emad A.
Green, Andrew R.
Band, Hamid
Band, Vimla
Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients
title Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients
title_full Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients
title_fullStr Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients
title_full_unstemmed Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients
title_short Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients
title_sort overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in her2/neu-overexpressing breast cancer patients
topic Preclinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397230/
https://www.ncbi.nlm.nih.gov/pubmed/22270930
http://dx.doi.org/10.1007/s10549-011-1946-8
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