Epithelial-to-mesenchymal transition (EMT) plays an important role in the development of the invasive and metastatic potentials of
breast cancer cells during progression. Human
biliverdin reductase (hBVR), an
enzyme in the
heme metabolism pathway, is involved in
hypoxia-induced renal tubular EMT. However, whether hBVR contributes to the EMT of
breast cancer remains unclear. Here, we used
breast cancer cell lines (MCF-7, T-47D) and normal breast epithelial cells (MCF-10A) to explore the potential role of hBVR in the EMT of
breast cancer. Western blot, RT-PCR and immunofluorescence were employed to test the expression and location of hBVR in the cell lines.
Small interfering RNA of hBVR (si-hBVR) was used to knockdown the expression of hBVR, and
U0126 was applied to inhibit the ERK1/2 signaling in MCF-7, T-47D cells. We found that hBVR highly expressed in MCF-7 and T-47D cells compared with MCF-10A cells, and had different cellular locations between them. Our results revealed that EMT occurred in tissues from
breast cancer patients and
breast cancer cell lines. However, the EMT in MCF-7 and T-47D cells was suppressed by si-hBVR and
U0126. Furthermore, the expression of phosphorylated ERK1/2 was down-regulated by si-hBVR. In addition, hBVR regulated EMT through the ERK1/2 signaling, but
bilirubin, which is a product of hBVR in the
heme metabolism pathway in
breast cancer, did not. Taken together, these findings provide new evidence that hBVR plays an important role in promoting EMT in human
breast cancer through the ERK1/2 signaling pathway, and hBVR may be a therapeutic target for this disease.