p-CREB-1 at Ser 133 is a potential marker for breast cancer

Z.-C. Xin, H.-W. Hu, Z.-H. Lao, L.-Q. Zhu, E. Biskup, H.-W. Zhang

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. zhang.hongwei@zs-hospital.sh.cn

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• Oncology

OBJECTIVE: Dysregulation of numerous oncogenes and their downstream signaling pathways, among others in the signaling transduction molecule p-CREB-1 (p-cAMP responsive element binding protein-1), is an essential feature of different types of cancer. To investigate whether p-CREB-1 is also pivotal in tumorigenesis and metastogenesis of breast cancer, we conducted a prospective study with long-term follow-up on 96 patients with breast cancer.

PATIENTS AND METHODS: Pathway array and tissue microarray (TMA) were used to detect the differential expression of CREB (cAMP-responsive element binding protein) and p-CREB-1 in breast cancer cells, breast cancer stem cells (BCSCs), human breast cancer tissues (BCTs), and adjacent normal tissues (ANTs). The associations between p-CREB-1 expression, clinicopathological variables, and survival rates of the patients were analyzed and calculated.

RESULTS: Our results revealed that p-CREB-1 and CREB expression in cancerous cell lines and tissues were significantly upregulated compared with non-cancerous cell lines and tissues. Most statistically significant overexpression was detected in BCSCs (p<0.01). In TMA and immunohistochemical analyses, BCTs exhibited significantly higher expression of p-CREB-1 and CREB than ANTs (p<0.001). Clinicopathological variable and survival analysis revealed a correlation between high expression (++/+++) of p-CREB-1 and the presence of axillary lymph node metastasis (p<0.05) and poorer disease-free and overall survival.

CONCLUSIONS: p-CREB-1 is a potential predictive and prognostic biomarker and a promising therapeutic target in breast cancer.

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