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Down-regulation of CacyBP is associated with poor prognosis and the effects on COX-2 expression in breast cancer
Fang Nie1, Xiao-Ling Yu, Xiao-Ge Wang
1Department of Respiratory Medicine, the Fourth Affiliated Hospital of China Medical University, Yuhong District, Shenyang City, Liaoning Province 110032, PR China.
Abstract:
Calcyclin-binding protein (CacyBP) is a tumor suppressor in gastric and renal cell carcinoma, but an oncogene in pancreatic cancer. However, the function of CacyBP in breast cancer has not been well elucidated. In this study, we explored the clinical relevance of CacyBP and investigated the relationship between CacyBP and COX-2 in breast cancer. Immunohistochemical analysis in 172 cases of breast tissues showed that the positive rate of CacyBP protein expression in normal breast tissues (NBT) (89.3%) was higher than that in invasive ductal carcinoma (IDC) (56.1%) (P<0.05). RT-PCR and Western blot analysis showed that CacyBP mRNA and protein expression were significantly lower in tumor tissues as compared to those in the corresponding non-tumorous tissues (P<0.05). The expression trend of COX-2 was opposite with CacyBP in breast carcinogenesis. Moreover, the CacyBP expression was significantly negatively associated with the COX expression in the 132 breast cancer samples (correlation coefficient = 0.505, P<0.001). The clinicopathological data analysis in 132 breast cancer samples showed that CacyBP expression was positively correlated with well differentiated samples (P=0.021), low pathologic TNM stage (P=0.009), and no lymphatic metastasis (P=0.027) of patients with breast cancer. Furthermore, reduced CacyBP expression was associated with poor prognosis. Knockdown of CacyBP gene using siRNA enhanced the proliferation and invasion ability of breast cancer cells, which was dependent on COX-2 expression. In conclusion, CacyBP regulation of COX-2 expression may play an important role in human breast carcinogenesis. Restoration of CacyBP gene is a potential therapeutic target of breast cancer.
Insights
Calcyclin-binding protein (CacyBP) is often reduced in breast cancer, correlating with poor prognosis and increased cell invasion. Its regulation of COX-2 suggests CacyBP as a potential therapeutic target for breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Calcyclin-binding protein (CacyBP) has a dual role as a tumor suppressor or oncogene depending on cancer type.
- Its specific function in breast cancer remains largely uncharacterized.
Purpose of the Study:
- To investigate the clinical significance of CacyBP in breast cancer.
- To explore the relationship between CacyBP and COX-2 in breast carcinogenesis.
Main Methods:
- Immunohistochemical analysis of 172 breast tissue samples.
- RT-PCR and Western blot to assess CacyBP mRNA and protein levels.
- Correlation analysis with clinicopathological data and COX-2 expression.
Main Results:
- CacyBP expression was significantly lower in invasive ductal carcinoma (IDC) compared to normal breast tissues.
- Reduced CacyBP expression correlated with poor differentiation, advanced TNM stage, lymphatic metastasis, and unfavorable prognosis.
- CacyBP expression was inversely associated with COX-2 expression.
- CacyBP knockdown enhanced breast cancer cell proliferation and invasion, dependent on COX-2.
Conclusions:
- CacyBP acts as a tumor suppressor in breast cancer, with its downregulation linked to disease progression.
- The inverse relationship between CacyBP and COX-2 suggests a regulatory role in breast carcinogenesis.
- Restoring CacyBP expression presents a potential therapeutic strategy for breast cancer.
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