Expression of NgBR Is Highly Associated with Estrogen Receptor Alpha and Survivin in Breast Cancer

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.

cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases

“…NgBR mRNA levels are increased in ductal adenocarcinoma and nonsmall cell lung carcinoma specimens (84,85). Clearly, regulation of glycosylation influences cell growth because the loss of ALG genes required for protein N-glycosylation triggers cell cycle arrest in yeast (86).…”

Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

“…In addition, studies showed that Nogo-B can be a promising parameter for lower malignancy in breast or lung carcinomas (Wang et al 2013;Pula et al 2014). Nogo-B expression indicates neuronal regeneration in the central nervous system, and was identical to that of the apoptosis-inducing gene in human carcinomas (Li et al 2001).…”

Comprehensive proteome quantification reveals NgBR as a new regulator for epithelial–mesenchymal transition of breast tumor cells

“…Our preliminary results show that overexpression of amino-terminal domain of Nogo-B (AmNogo-B) does not cause any significant effects on tumor cell growth and cell survival (data not shown). Knockdown of NgBR also does not significantly affect the growth and survival of MCF-7 cells under basal growth condition [28]. The detailed roles of NgBR in breast cancer really need further investigation.…”

“…Genetic knockdown of either NogoB or NgBR by antisense morpholino abolished intersomitic vessel formation during developmental angiogenesis, and those defects can be rescued by constitutively activated Akt [27]. Our recent studies further demonstrated that NgBR is highly expressed in human breast invasive ductal carcinoma [28]. However, the exact roles of NgBR in the progression of cancer are still unclear.…”