Reduced expression of activin receptor-like kinase 7 in breast cancer is associated with tumor progression

To explore the clinical implication of activin receptor-like kinase 7 (ALK7) expression in breast cancer, we evaluated its protein level in six kinds of human breast tissue samples, including adjacent normal tissues, adenosis, breast fibroadenoma, ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and lymph node metastases (LNM). Immunohistochemical analyses showed that ALK7 was more frequently and much more intensely expressed in adjacent normal tissues, adenosis, and fibroadenoma tissues than in malignant tissues (DCIS, IDC, and LNM). Furthermore, the ALK7 expression in primary tumors and the corresponding LNM was evaluated in parallel samples from 60 patients with IDC. Results showed that the ALK7 expression status in primary tumors and LNM was concordant in 53 patients (88%), suggesting that ALK7 expression was retained in LNM. Moreover, our results suggested that ALK7 expression inversely correlated with the tumor grade (P = 0.009) and clinical stage (P = 0.004) in IDC significantly. Finally, the effect of activin-ALK7 pathway on the breast cancer cell growth was elucidated, and results revealed that overexpression of ALK7 could restore the inhibitory effect of activin B on the growth of ALK7-negative breast cancer cell line, ZR-75-30. These findings provide the evidence that the reduction or lack of ALK7 expression may account for the loss of its ligand sensitivity of breast cancer cells, thereby leading to breast tumor progression.