ErbB/Her dimerization in breast and lung cancer

Abstract

643 Background: Transmembrane receptor tyrosine kinases play an important role in the pathogenesis of many types of cancer. The EGFR family includes erbB1 (EGFR or Her1), erbB2 (Her2 or neu), erbB3 (Her3), and erbB4 (Her4). It is well established that ligands like EGF and HRG bind to the extracellular region of the EGFR monomers and promote receptor dimerization. Receptor dimerization leads to increased tyrosine kinase activity resulting in uncontrolled cell proliferation and inhibition of apoptosis. We have developed a method for the determination of Her dimerization patterns in cancer using eTag™ multiplexed assays. Materials and Method: We have analyzed a total of 73 snap-frozen human breast tissues and 37 lung tissues comprising of both tumor and normal samples. Using the proximity-based multiplexed eTag assays, we determined the dimerization profiles in these tissues. Results: ErbB/Her dimerization was detected only in tumor tissues but not in normal breast tissues, whether matched with the same donor or not. Out of the 31 breast tumor samples analyzed, Her1/2 dimers were detected in 20 tumor samples. Her-2/3 dimers were detected in 29 out of 43 tumor samples. We also found that all tumor samples had higher Her-2 levels compared to normal breast samples. In addition, we detected Her-2/2 homodimers in 27 out of 43 tumor samples. In lung tissues, seven out of 27 tumors had Her1/1 dimers while four out of 27 tumors had Her1/2 dimers, indicating that the predominant dimerization types in lung are Her1/1 and Her1/2. Our quantitative dimerization assays showed that the total receptor expression levels and dimerization profiles were different in different tumor samples both in lung and breast samples. Conclusion: eTag technology can offer a valuable prognostic and quantitative tool for stratifying cancer patients for targeted therapy. In addition, eTag technology can help in assessing the activation state of the receptor during the course of patient treatment. No significant financial relationships to disclose.