Title:Reduced Expression of RBP7 is Associated with Resistance to Tamoxifen In Luminal
A Breast Cancer
Volume: 23
Issue: 8
Author(s): Xiaolu Yan*, Zhe Gao, Lixia Zhang and Chuan Chen*
Affiliation:
- Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei, China
- College of Life Science, Institute of Life Science and Green
Development, Hebei University, Baoding, Hebei, China
Keywords:
Breast cancer, RBP7, luminal A subtype, tamoxifen, resistant, retinol.
Abstract:
Background: Tamoxifen is the most commonly used hormonal treatment for ERĪ±-positive breast cancer.
Tamoxifen resistance is still a big problem for ERĪ± target therapy. RBP7 is a member of the cellular retinol-binding
protein family.
Objective: This study aims to investigate the prognostic role of RBP7 and the relationship between RBP7 expression
and sensitivity or resistance to tamoxifen in ERĪ±-positive breast cancer.
Methods: A bioinformatics method was used to investigate RBP7 expression and the prognostic value of RBP7 in
different subtypes of breast cancer. The relationship between RBP7 expression and sensitivity or resistance to tamoxifen
was studied using clinical data (GSE1379) and cell line data (GSE27473, GSE2645923, GSM3715281, and
GSM3715282). Transfection of RBP7 experiments was used to testify to the function of RBP7 in MCF7 cell.
Results: RBP7 is a member of the family of cellular retinol-binding proteins. RBP7 expression was down-regulated at
both mRNA and protein levels in breast cancer and was not associated with different TNM (Tumor, Node, Metastasis)
stages. High expression of RBP7 was significantly related to good relative percent survival in the luminal A subtype,
but in negative breast cancer, the result was opposite. The ROC plot showed that RBP7 had a significant predictive
value for the tamoxifen response in the luminal A subtype. The expression of RBP7 from patients with recurrence
treated with tamoxifen was significantly reduced. Gene Expression Omnibus showed that RBP7 expression was reduced
considerably in tamoxifen-resistant MCF7 cells and T47D cells. The expression of RBP7 was positively correlated
with some microRNAs involved in negatively regulating tamoxifen-resistant breast cancer. We also found that
the expression of RBP7 decreased significantly in tamoxifen-resistant MCF7 cells, and transfection of RBP7 increased
the sensitivity of resistant cells to tamoxifen.
Conclusion: Reduced expression of RBP7 is associated with resistance to tamoxifen in luminal A breast cancer. Our
research may help to explore the mechanisms of resistance of breast cancer to tamoxifen.
