Nogo-B and NgBR Are Strongly Associated with Luminal A Sub-Type Breast Cancer
Bei Wang, Baofeng Zhao, Jian Huang, Robert Q Miao. China-Japan Friendship Hospital, Beijing, China; Medical College of Wisconsin, Milwaukee, WI
Background: NgBR is a type I receptor with a single transmembrane domain and was identified as a specific receptor for Nogo-B. Our previous work has shown that axon guidance gene family Nogo-B and its receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial cells in vitro and blood vessel formation in zebrafish. Our recent findings further demonstrated that NgBR can bind and recruit farnesylated Ras to plasma membrane, which is a critical step required for the activation of Ras signaling in human breast cancer cells and tumorigenesis.
Design: Here, we use immunohistochemistry (IHC) and real-time PCR approaches to examine the expression and localization of Nogo-B and NgBR in two cohorts of 400 cases of breast invasive ductal carcinoma (IDC) arranged on tissue microarray slides. Expressions of ER-alpha,PR,HER2,CK5,CK5/6,CK14,EGFR and Survivin were also examined using IHC in these tumors. Data were analyzed using statistical software SPSS 16.0 for Windows. The relationship was tested using Pearson Chi-square tests. A P-value<0.05 is defined as statistical significance.
Results: NgBR and Nogo B proteins were detected in the most of epithelial and myoepithelial cells in the normal breast tissues, as well as in interstitial blood vessels. Expression of Nogo-B and NgBR in tumor cells is much stronger than in normal breast epithelial cells. The breakdown of the distribution of NgBR in breast tumors was as follows: 36.5% negative, 30.3% weak and 33.3% strong, respectively. The breakdown of the distribution of Nogo-B in tumors was as follows: 8.2% negative, 23.5% weak and 68.2% strong, respectively. The results further indicated that NgBR and Nogo-B are highly expressed in ER alpha-positive, HER2-negative and CK5-negative IDC, and strongly associated with luminal A sub-type breast cancer (P<0.001). Striking, Nogo-B and NgBR are also strongly associated with the expression of survivn, which is a well-known apoptosis inhibitor (P<0.0001). The correlation between NgBR and survivin was further confirmed by real-time PCR analysis using normalized breast cancer cDNA arrays from Origene.
Conclusions: Nogo-B and NgBR are new molecular markers for breast cancer, particularly for luminal A sub-type breast cancer. The data suggest that the expression of Nogo-B and NgBR may be essential in promoting tumor cell proliferation via survivin in breast cancer. Therefore, Nogo-B and NgBR may be a novel target for treatment of breast cancer.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 21, Wednesday Afternoon