Human biliverdin reductase promotes EMT through the ERK1/2 signal pathway in breast cancer.
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.
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing 163319, China.
Min
M
Zhang
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing 163319, China.
Shasha
S
Song
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing 163319, China.
Zhi
Z
Yi
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing 163319, China.
Xijuan
X
Zhao
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing 163319, China.
Li
L
Fu
Department of Pathology, Harbin Medical University, No. 39 Xinyang, Daqing 163319, China.
Lin
L
Wang
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing 163319, China; Department of Immunology, College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing 163319, China.
Cui
C
Ma
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing 163319, China.
Min
M
Mao
Department of Pharmacology, College of Basic Medicine, Harbin Medical University, Daqing 163319, China.
Yan
Y
Xing
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Daqing 163319, China; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China. Electronic address: dalingz@yahoo.com.
Daling
D
Zhu
D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System; D058990:Molecular Targeted Therapy; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
D034741:RNA, Small Interfering; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase
Bilirubin; Breast cancer; EMT; ERK1/2 signal pathway; hBVR