Dr. Antje Anji
Our team aims to better understand the regulation of N-methyl-D-aspartate (NMDA) receptor gene expression following chronic exposure to alcohol. Although these receptors, which belong to the family of glutamate receptors that mediate excitatory neurotransmission, are predominantly found in the central nervous system, findings of their expression in non-neuronal tissues are increasing. Functional NMDA receptors require assembly of the NR1 subunit with members of the NR2 and/or the NR3 family. Recently, the NR1 and NR2B receptor subunits were identified in ‘high grade’ breast cancer cell lines and breast cancer tissue. Similarly, functional NMDA receptors have been detected in small-cell lung cancer cell lines and esophageal squamous cell carcinoma.
The expression of the NR2B receptor subunit appears to be silenced by hypermethylation in esophageal, gastric and breast cancers, suggesting that the expression of functional NR2B subunits is associated with suppression of tumor growth. In particular, promoter CpG island methylation of the NR2B gene is associated with progression from non-invasive to invasive breast cancer, highlighting the importance of epigenetic changes in tumor progression. We are interested in understanding the mechanisms—such as methylation of CpG dinucleotides (epigenetic mechanisms), involvement of cis-acting sequences, transcription factor regulation, and positioning of nucleosomes—involved in regulation of NR2B gene transcription in breast cancer.