Abstract: Background and purpose: Thyroid hormone and its receptors are closely related to breast cancer. Thyroid receptor-interacting protein 6 (TRIP6) may promote the occurrence and development of breast cancer by interacting with thyroid receptor. This study aimed to investigate the role of TRIP6 in breast cancer and its possible mechanism. Methods: Immunohistochemical staining was used to detect the expressions of TRIP6 and the transcription factor forkhead box C1 (FOXC1) in 268 breast cancer tissues, their matched adjacent tissues and 80 benign fibroadenoma tissues that were resected in Shandong Cancer Hospital from January 2011 to December 2013. COX proportional hazards regression model and Kaplan-Meier method were used to analyze the survival prognosis of breast cancer patients. The expressions of TRIP6 and FOXC1 in normal breast epithelial cells MCF-10A and breast cancer cells (BT474, MCF7 and MDA-MB-231) were detected by Western blot. MDA-MB-231 cells were transfected with TRIP6 si-RNA and si-control respectively, and cell proliferation was detected by clone formation experiment and cell counting kit-8 (CCK-8) experiment. Cell invasion was detected by transwell cell experiment. Cell migration was detected by cell scratch experiment. Western blot was used to detect relative expression of FOXC1 protein. Results: The positive expression rates of TRIP6 and FOXC1 in breast cancer tissues were 85.08% and 88.06%, respectively, which were higher than those in benign fibroadenoma (25.00% and 15.00%) and paracancerous tissues (55.97% and 62.31%) (all P<0.01). The positive expression rates of TRIP6 and FOXC1 in breast cancer tissues were positively correlated (r=0.771, P<0.001). High expressions of TRIP6 and FOXC1 were independent factors affecting the overall survival and progression-free survival of breast cancer patients (both P<0.05). The overall survival rate and progression-free survival rate of breast cancer patients with high expression of TRIP6 were lower than those of patients with low expression of TRIP6 (all P<0.001). The overall survival rate and progression-free survival rate of breast cancer patients with high expression of FOXC1 were lower compared with patients with low expression of FOXC1 (all P<0.001). The relative protein expression levels of TRIP6 and FOXC1 were higher in BT474, MCF7 and MDA-MB-231 cells than in MCF10A cells (all P<0.05). The relative protein expressions of TRIP6 and FOXC1 in MDA-MB-231 cells were positively correlated (r=0.908, P=0.033). The number of cloned cells, proliferation viability, cell invasion, cell migration rate and relative protein expression of FOXC1 were all lower in the TRIP6 si-RNA group than in the si-control group (all P<0.05). Conclusion: TRIP6 may participate in the occurrence and development of breast cancer through FOXC1, and its high expression indicates that the survival prognosis of patient is poor.

Key words: Thyroid receptor-interacting protein 6, Forkhead box C1, Breast cancer, Proliferation, Invasion, Migration, Prognosis