Abstract
Calcineurin B homologous protein isoform 2 (CHP2), an essential cofactor for Na+/H+ exchanger isoform 1 (NHE1), is identified to be expressed in various malignant cell lines. However, the clinical significance and biological role of CHP2 in breast cancer remain to be established. Here, CHP2 was markedly overexpressed in breast cancer cells and clinical tumor specimens. Immunohistochemical analysis revealed that the expression of CHP2 was significantly correlated with patients' clinicopathologic characteristics like clinical stage, and breast cancer patients with high CHP2 expression had shorter overall survival compared with patients with low CHP2 expression. Moreover, it was demonstrated that overexpressing CHP2 significantly enhanced, whereas silencing endogenous CHP2 inhibited, the proliferation and tumorigenicity of breast cancer cells in vitro and in vivo In addition, overexpression of CHP2 accelerated, whereas inhibition of CHP2 retarded, G1-S phase cell-cycle transition in breast cancer cells. Mechanistically, overexpression of CHP2 activated AKT signaling and suppressed the transactivation of the forkhead box O3 (FOXO3/FOXO3a) transcription factor.Implications: This study discovers a previously unrecognized role of CHP2 in the progression of breast cancer and supports the significance of this gene as a novel prognostic biomarker and a potential therapeutic target for breast cancer. Mol Cancer Res; 16(10); 1512-22. ©2018 AACR.
Highlights
Breast cancer is the second most common cancer in the world, and the incidence of female breast cancer has continuously increased [1]
Real-time PCR and Western blotting analyses were performed, and the results showed that Calcineurin B homologous protein isoform 2 (CHP2) mRNA and protein expression were markedly upregulated in all the tested breast cancer cell lines compared with human mammary epithelial cells (HMEC; Fig. 1A and B)
These results indicated that CHP2 expression was upregulated in breast cancer
Summary
Breast cancer is the second most common cancer in the world, and the incidence of female breast cancer has continuously increased [1]. Despite the progress in early detection and use of new therapeutic targets, breast cancer remains a major problem in public health [2]. The discovery of new molecular actors involved in the regulation of breast cancer development is essential to improve the management of this disease. Understanding the roles and molecular mechanisms of these molecular actors may provide new insights into the physiology and pathology of breast cancer and enable the development of novel and effective anticancer therapeutics. Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).
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