Summary: | 碩士 === 國立陽明大學 === 口腔生物研究所 === 99 === L-selectin (SELL) belongs to selectin protein family, and highly expresses in leukocyte, which plays an important role in adhesion between leukocytes and vascular endothelial cells. Oral squamous cell carcinoma (OSCC) is a common worldwide malignancy. Our previous study showed that the expression of SELL in OSCC cells, and metastatic lesions had higher SELL expression than those from primary OSCC. Patients with higher SELL expression in metastatic lesion have lower survival rate than contrasting patient group. We also showed the increased of cell migration and tumor metastasis by expressing SELL. However, the regulation of SELL in OSCC is unclear.
In this study, we investigate how SELL is regulated in OSCC cells. We constructed reporter plasmids with different lengths of SELL promoter regions, to find the most important region -131~+35 bp that regulate SELL expression and this particular region can be affected with TNF-α treatment. Moreover, predicted two transcription factor binding site, GATA-1 and NF-κB, in this promoter region. Therefore, using the mutant reporter plasmids, we indicated that GATA-1 is a positive regulator in SELL promoter region. However, NF-κB binds on the SELL promoter region and regulates SELL transcription. Lastly, we identified the decrease of migration and anchorage independent growth ability of OSCC cells modulated SELL down-regulation.
In summary, SELL expression is regulated by NF-κB, and plays a crucial role in the mobility and metastasis of OSCC cells.
|