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 G1 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.
Highlights
As a negative regulator of thioredoxin (TRX), thioredoxin interaction protein (TXNIP) ( known as Vitamin D3 up-regulated protein 1 (VDUP-1) or thioredoxin binding protein 2 (TBP-2)) has strong growth suppressive, metastasis inhibitory and proapoptotic functions [1]
We found that high TXNIP or p27 expression was associated with better overall survival (OS) (Figure 1B, P=0.001 and P=0.012)
We found a significant negative correlation between TXNIP and Her-2 status in breast cancer, and showed that inhibition of the Her-1/2 pathway resulted in increased TXNIP expressions
Summary
As a negative regulator of thioredoxin (TRX), thioredoxin interaction protein (TXNIP) ( known as Vitamin D3 up-regulated protein 1 (VDUP-1) or thioredoxin binding protein 2 (TBP-2)) has strong growth suppressive, metastasis inhibitory and proapoptotic functions [1]. It has been identified as a tumor suppressor gene in various solid tumors and hematological malignancies, including breast cancer [2]. A recent study on the association of TXNIP expression and metastasis-free survival of breast cancer patients found that TXNIP was associated with better prognosis [2] They induced Her-2 in MCF-7 cells, which strongly inhibited TXNIP expression, following a strong increase reactive oxygen species levels. As a major redox regulator, TXNIP has recently been proposed as a therapeutic target for cancer treatment [4]
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