Secreted CLU is associated with the initiation of triple-negative breast cancer

Abstract

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.

Keywords: :

• human triple-negative breast cancer
• secreted clusterin
• spontaneous breast cancer
• TA2 mouse

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This study was supported by the Key Project of National Nature Science Foundation of China (No. 30830049), the National Nature Science Foundation of China (No. 30770828), the co-operation of China-Sweden (No. 09ZCZDSF04400), the Tianjin Natural Science Foundation (No. 09JCYBJC12100), and the 973 Program from the Ministry of Science and Technology of China (No. 2011CB933104). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.