Title: 2148 - The Role of MECT1-MAML2 Fusion Protein in Mucoepidermoid Carcinoma
Esra Amoura (Presenter)
Universtiy of Sheffiled
Keith Hunter, School of Clinical Dentistry, University of Sheffield
Colin Bingle, University of Sheffield
Lynne Bingle, School of Clinical Dentistry, University of Sheffield
Mucoepidermoid carcinoma (MEC) is the most common salivary gland cancer. A significant proportion of MEC cases (≥50%) have been associated with a unique and recurrent gene translocation which results in the production of the MECT1-MAML2 fusion protein. Although the presence of this fusion protein could play a crucial role in tumour development and growth, its molecular pathogenesis remains elusive. The aim of this study was to try to understand the role of the MECT1-MAML2 fusion protein in MEC, to investigate its effect on the expression of CREB and NOTCH target genes and its ability to transform cells.
To further understand the biological basis of the fusion protein we have generated an epitope tagged MECT1-MAML2 expression clone by amplifying the fusion gene from MEC-expressing cell lines (NCIH292 and UM-HMC).
The MECT1-MAML2 expression clone was transfected into a lung carcinoma cell line and primary salivary gland cells, isolated from human explanted tissues, to study the down-stream effects of fusion protein expression.
A three-dimensional (3D) organoid model of salivary glands was developed to validate the monolayer cell culture results.
Results: Flag and Myc tagged mammalian expression constructs have been successfully generated and verified with overlapping sequences to indicate 100% identity to the subject.
Primary salivary gland cells were successfully transfected; however, greater transfection efficiency was achieved with the mucoepidermoid cell line.
A 3-D organoid model, including a folded duct-like cell structure, has been developed following 14 days in culture.
Conclusions: We now have a number of valuable tools which will allow us to fully elucidate the role of the MECT1-MAML2 fusion protein in MEC tumorigenesis.
This abstract is based on research that was funded entirely or partially by an outside source:
The Minstry of Higher Education, Tripoli, Libya
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE