Identification of the CREB-regulated transcriptional program in human mucoepidermoid carcinoma cells

Mucoepidermoid carcinomas (MEC) is the most common salivary gland malignancy. To date, advanced and nonresectable MEC have poor prognosis and no effective treatment. The CRTC1-MAML2 fusion oncogene, which is associated with more than 50% of MEC, consists of the N-terminal CREB-binding domain of the CREB transcriptional co-activator CRTC1 and the C-terminal transcriptional activation domain of the Notch transcriptional co-activator MAML2. CRTC1-MAML2 fusion was found to interact with CREB and constitutively activate their transcriptional targets. To investigate the contribution of the transcription factor CREB to mediate the fusion target gene expression, gene expression profiling analysis were performed in two salivary gland tumor cell lines (including fusion-positive H3118 MEC cells and fusion-negative HSY parotid adenocarcinoma cells) before and after CREB knockdown. This study demonstrated that CRTC1-MAML2 co-activation of CREB is a major mechanism underlying CRTC1-MAML2-mediated transcriptional regulation.

12

Chen J, Li JL, Chen Z, Griffin JD, Wu L