Phosphatidylinositol 3-kinase p110δ expression in Merkel cell carcinoma
Research output: Contribution to journal › Article › Academic › peer-review
The prognosis of stage III/IV Merkel cell carcinoma (MCC) is very poor. The Phosphatidylinositol 3-kinase p110? specific inhibitor idelalisib has recently been reported to induce complete clinical remission in a stage IV MCC patient. Here we assessed the expression of p110? in primary MCC and MCC cell lines including its functionality. Immunofluorescence microscopy revealed a specific cytoplasmic p110? expression in 71.4% of the tested MCCs and in all tested MCC cell lines. Compared to the B cell leukemia cell line REH all MCC cell lines, except MKL-1, revealed a lower response towards the treatment with idelalisib. MKL-1 showed a 10-fold higher IC50 compared to REH which was accompanied by a significant decrease of Akt phosphorylation. However, treating the MCC cells with the specific PI3K p110? subunit inhibitor BYL719 led to a more effective decrease of the cell viability compared to idelalisib: WaGa cells 30-fold, PeTa cells 15-fold and all other MCC cell lines 3-fold. Although PI3K p110? is expressed in the majority of MCCs and cell lines its inhibition by idelalisib alone does not suffice to effectively affect MCC cells viability.
Chteinberg, E., Rennspiess, D., Sambo, R., Tauchmann, S., Kelleners-Smeets, N. W. J., Winnepenninckx, V., Speel, E., Kurz, A. K., Zenke, M., & zur Hausen, A. (2018). Phosphatidylinositol 3-kinase p110δ expression in Merkel cell carcinoma. Oncotarget, 9(51), 29565-29573. https://doi.org/10.18632/oncotarget.25619