TY - JOUR
T1 - Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer
T2 - A marker of poor prognosis in HER2/neu-overexpressing breast cancer patients
AU - Zhao, Xiangshan
AU - Mirza, Sameer
AU - Alshareeda, Alaa
AU - Zhang, Ying
AU - Gurumurthy, Channabasavaiah B
AU - Bele, Aditya
AU - Kim, Jun Hyun
AU - Mohibi, Shakur
AU - Goswami, Monica
AU - Lele, Subodh M
AU - West, William
AU - Qiu, Fang
AU - Ellis, Ian O.
AU - Rakha, Emad A.
AU - Green, Andrew R.
AU - Band, Hamid
AU - Band, Vimla
N1 - Funding Information:
Acknowledgments This research was supported by the NIH grants CA96844 and CA144027 and Department of Defense grants W81XWH-07-1-0351 and W81XWH-11-1-0171 to V.B; the NIH grants CA87986, CA105489, CA99163, CA116552 and NCI 5U01CA151806-02 to H.B; and the NCI Core Support Grant to UNMC-Eppley Cancer Center. S.M and A.B are supported by a Susan G. Komen Postdoctoral Fellowship (KG111248) and a DOD predoctoral fellowship (W81XWH-11-1-0020), respectively. This work was initiated while the last author was on the faculty of Evanstan Northwestern Healthcare at Northwestern, Evanston, IL.
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Cell cycle
KW - DCIS
KW - Ecdysoneless
KW - HER2/neu
KW - IDC
UR - http://www.scopus.com/inward/record.url?scp=84863925514&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863925514&partnerID=8YFLogxK
U2 - 10.1007/s10549-011-1946-8
DO - 10.1007/s10549-011-1946-8
M3 - Article
C2 - 22270930
AN - SCOPUS:84863925514
SN - 0167-6806
VL - 134
SP - 171
EP - 180
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -