Advances in Brief The Tumor Suppressor Gene LKB1 Is Associated with Prognosis in Human Breast Carcinoma

Purpose: LKB1 (also called STK11) is a recently identified tumor suppressor gene in which its mutation can lead to Peutz-Jeghers syndrome, characterized by gastrointestinal polyps and cancers of different organ systems. Weak expression of this gene does occur at a certain frequency in sporadic breast cancer. This indicates that LKB1 gene may relate to the tumorigenesis of breast cancer. Experimental Design: To investigate the function of the LKB1 gene in sporadic breast cancer, we reintroduced LKB1 into breast cancer cell lines which lack the LKB1 gene. Also, we examined the LKB1 protein expression in human breast cancer samples. Results: We found that reintroducing LKB1 into breast cancer cell lines suppresses cell growth by G1 cell cycle block. The LKB1-mediated G1 cell cycle arrest is caused by up-regulation of the expression of p21 in breast cancer MDA-MB-435 cells. We also demonstrated that low LKB1 protein expression correlates with higher histological grade (P 0.013), larger tumor size (P 0.001), progesterone receptor status (P 0.048), and presence of lymph node metastasis (P 0.003). Furthermore, LKB1 low expression was associated with a higher relapse rate (P 0.002) and a worse OS (P 0.008). Conclusions: LKB1 plays a role in tumor suppressor function in human breast cancer. LKB1 expression may be a useful prognostic marker in human breast cancer.