Secreted CLU is associated with the initiation of triple-negative breast cancer.
Triple-negative breast cancer, which is negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, represents about 15-26% of all breast cancer cases. However, because of its genotype, a triple-negative disease accounts for a remarkable metastasis and mortality. Moreover, no targeted treatment is available because the molecular mechanism of triple-negative breast cancer initiation is still unclear. Secreted clusterin (sCLU) is associated with the refractory to anti-estrogen in breast cancer cells. We investigated the sCLU expression in 384 human breast cancer cases, including 61 triple-negative cases, as well as the relationship between sCLU and clinical pathological characteristics. Triple-negative patients (75.4%) were positive for sCLU based on immunohistochemical analysis, and sCLU expression in this subtype was proven related to a larger tumor size, an axillary node status, and a higher clinical stage. Furthermore, we used a spontaneous breast cancer mouse strain with a triple-negative genotype to detect the sCLU dynamic expression in breast cancer oncogenesis using western blot and real-time polymerase chain reaction. The sCLU mRNA and protein expression in the tumor and hyperplastic epithelium were upregulated and reached a peak compared with those of a normal mammary gland. These results suggest that sCLU is involved in the initiation of triple-negative breast cancer, which is beneficial for the clinical trial design of an anti-CLU treatment for triple-negative breast cancer.
Department of Pathology, Tianjin Medical University, Tianjin, China.
Danfang
D
Zhang
Baocun
B
Sun
Xiulan
X
Zhao
Yanfen
Y
Cui
Shaoyan
S
Xu
Xueyi
X
Dong
Jianmin
J
Zhao
Jie
J
Meng
Xiaohua
X
Jia
Jiadong
J
Chi
D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051152:Clusterin / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006801:Humans; D051379:Mice; D016019:Survival Analysis
D051152:Clusterin