Cullin-1 promotes cell proliferation in human breast cancer and is related to diabetes.
OBJECTIVE
Breast carcinoma (BCA) and diabetes mellitus (DM) are two major health problems in women and the general population. Cullin-1 is reported to be an important tumor-related protein involved in cell-cycle progression, signal transduction and transcription. The aim of this work is to investigate the role of Cullin-1 in the development of BCA and to find potential relationships between Cullin-1 and diabetes in BCA patients.


METHODS
To evaluate the function of Cullin-1, we entered 168 patients with primary invasive BCA in this study. Pairs of BCA tissues and adjacent noncancerous tissues from these patients were collected between 2006 and 2008. We used immunohistochemistry to analyze the correlation between Cullin-1 expression and clinicopathological variables and patient survival. In addition, we investigated the role of Cullin-1 in BCA cell proliferation.


RESULTS
Cullin-1 expression was upregulated in BCA tissues. Enhanced immunoreactivity for Cullin-1 in BCA tissues was inversely correlated with overall survival and disease-free survival, which suggested a poor prognosis in BCA patients. Strong expression of Cullin-1 was more frequently observed in patients with estrogen receptor negativity and HER2 positivity. We also found that Cullin-1 expression was increased in BCA patients with a previous diagnosis of diabetes.


CONCLUSIONS
Our results demonstrate that increased Cullin-1 expression is significantly correlated with poor prognosis in patients with BCA. Cullin-1 might regulate BCA cell proliferation through the ubiquitin-proteasome system. Thus, Cullin-1 might be an important marker and a therapeutic target in BCA.
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou - P.R. China.|Department of General Surgery and Transitional Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi - P.R. China.
Yun-Hai
YH
Zhou
Department of General Surgery and Transitional Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi - P.R. China.
Jiazeng
J
Xia
Department of Oncology, the Affiliated Hospital of Jiangnan University, Wuxi - P.R. China.
Wen-Huan
WH
Xu
Department of General Surgery and Transitional Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi - P.R. China.
Xiqi
X
Zhu
Department of Oncology, the Affiliated Hospital of Jiangnan University, Wuxi - P.R. China.
Xiao-Hong
XH
Wu
Department of Oncology, the Affiliated Hospital of Jiangnan University, Wuxi - P.R. China.
Dong
D
Hua
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou - P.R. China.
Chungen
C
Xing
D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D044842:Cullin Proteins / Q000096:biosynthesis*; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C100318:Cullin 1; D044842:Cullin Proteins