TXNIP interaction with the Her-1/2 pathway contributes to overall survival in breast cancer.

// Weiwei Nie 1,* , Weisun Huang 1,* , Wenwen Zhang 2 , Jing Xu 2 , Wei Song 1 , Yanru Wang 1 , Aiyu Zhu 1 , Jiayan Luo 2 , Guichun Huang 2 , Yucai Wang 3 and Xiaoxiang Guan 1,2 1 Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, P.R. China 2 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R. China 3 Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA * These authors contributed equally to this work Correspondence: Xiaoxiang Guan, email: // Keywords : TXNIP, p27, Her-1/2 inhibitor, breast cancer Received : November 07, 2014 Accepted : December 24, 2014 Published : December 30, 2014 Abstract Previous studies have indicated that Her-2 induction causes a strong decrease in thioredoxin interaction protein (TXNIP) in breast cancer cells. However, little is known regarding the prognostic value of TXNIP in clinical breast cancer patients with anti-Her-2 treatment. Using a tissue microarray, we detected TXNIP and p27 expression in breast cancer tissue, as well as corresponding noncancerous tissues. We found that TXNIP expression was associated with better overall survival (OS) in these 150 breast cancer patients and that TXNIP and Her-2 expression status were significantly inversely correlated (r=-0.334, P <0.001). These results were validated in another 101 breast cancer tissue samples (r=-0.422, P <0.001). Moreover, TXNIP expression increased significantly following treatment of the human breast cancer cell lines BT474 and SK-BR-3 with a Her-1/2 inhibitor. Furthermore, TXNIP transfection induced p27 expression and G 1 cell cycle arrest and apoptosis. Taken together, our findings suggest that TXNIP plays a critical role in anti-Her-1/Her-2 treatment and may be a potential prognostic marker in breast cancer.