Expression of NgBR is highly associated with estrogen receptor alpha and survivin in breast cancer

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...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e78083-e78083
Main Authors: Wang, Bei, Zhao, Baofeng, North, Paula, Kong, Amanda, Huang, Jian, Miao, Qing Robert
Format: Article
Language:English
Subjects:
17β-Estradiol
Analysis
Angiogenesis
Apoptosis
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer
Cancer screening
Carcinoma, Ductal, Breast - metabolism
Carcinoma, Ductal, Breast - pathology
Cell Line, Tumor
Cell proliferation
Correlation
Epithelium - metabolism
ErbB-2 protein
Estradiol
Estrogen
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogen receptors
Estrogens
Female
Gene Expression
Humans
Immunohistochemistry
Inhibitor of Apoptosis Proteins - genetics
Inhibitor of Apoptosis Proteins - metabolism
Myelin Proteins - metabolism
Neoplasm Staging
Nogo protein
Nogo Proteins
Pathology
Pediatrics
Peptides
Phenols (Class of compounds)
Ras protein
Real time
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Sex hormones
Signal transduction
Signaling
siRNA
Statistical analysis
Surgery
Survivin
Tissue Array Analysis
Tissues
Tumor cells
Tumorigenesis
Tumors
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0078083