Faculty Collaboration Database

Expression of NgBR is highly associated with estrogen receptor alpha and survivin in breast cancer. PLoS One 2013;8(11):e78083

Date

11/14/2013

Pubmed ID

24223763

Pubmed Central ID

PMC3817177

DOI

10.1371/journal.pone.0078083

Scopus ID

2-s2.0-84892393422 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

NgBR is a type I receptor with a single transmembrane domain and was identified as a specific receptor for Nogo-B. Our recent findings demonstrated that NgBR binds farnesylated Ras and recruits Ras to the plasma membrane, which is a critical step required for the activation of Ras signaling in human breast cancer cells and tumorigenesis. Here, we first use immunohistochemistry and real-time PCR approaches to examine the expression patterns of Nogo-B and NgBR in both normal and breast tumor tissues. Then, we examine the relationship between NgBR expression and molecular subtypes of breast cancer, and the roles of NgBR in estrogen-dependent survivin signaling pathway. Results showed that NgBR and Nogo-B protein were detected in both normal and breast tumor tissues. However, the expression of Nogo-B and NgBR in breast tumor tissue was much stronger than in normal breast tissue. The statistical analysis demonstrated that NgBR is highly associated with ER-positive/HER2-negative breast cancer. We also found that the expression of NgBR has a strong correlation with the expression of survivin, which is a well-known apoptosis inhibitor. The correlation between NgBR and survivin gene expression was further confirmed by real-time PCR. In vitro results also demonstrated that estradiol induces the expression of survivin in ER-positive T47D breast tumor cells but not in ER-negative MDA-MB-468 breast tumor cells. NgBR knockdown with siRNA abolishes estradiol-induced survivin expression in ER-positive T47D cells but not in ER-negative MDA-MB-468 cells. In addition, estradiol increases the expression of survivin and cell growth in ER-positive MCF-7 and T47D cells whereas knockdown of NgBR with siRNA reduces estradiol-induced survivin expression and cell growth. In summary, these results indicate that NgBR is a new molecular marker for breast cancer. The data suggest that the expression of NgBR may be essential in promoting ER-positive tumor cell proliferation via survivin induction in breast cancer.

Author List

Wang B, Zhao B, North P, Kong A, Huang J, Miao QR

Authors

Amanda L. Kong MD, MS Professor in the Surgery department at Medical College of Wisconsin
Paula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biomarkers, Tumor
Breast Neoplasms
Carcinoma, Ductal, Breast
Cell Line, Tumor
Epithelium
Estrogen Receptor alpha
Female
Gene Expression
Humans
Inhibitor of Apoptosis Proteins
Myelin Proteins
Neoplasm Staging
Nogo Proteins
Receptors, Cell Surface
Tissue Array Analysis