Phosphatidylinositol 3-kinase p110δ expression in Merkel cell carcinoma
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Emil Chteinberg1,2,3, Dorit Rennspiess1, Ryan Sambo1, Samantha Tauchmann1, Nicole W.J. Kelleners-Smeets4, Véronique Winnepenninckx1, Ernst-Jan Speel1, Anna Kordelia Kurz5, Martin Zenke2,3 and Axel zur Hausen1
1Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
2Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Hospital, Aachen, Germany
3Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany
4Department of Dermatology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
5Department of Internal Medicine IV, RWTH Aachen University Hospital, Aachen, Germany
Axel zur Hausen, email: [email protected]
Keywords: Merkel cell carcinoma; phosphatidylinositol 3-kinase; chemotherapeutics
Received: February 05, 2018 Accepted: May 31, 2018 Published: July 03, 2018
The prognosis of stage III/IV Merkel cell carcinoma (MCC) is very poor. The Phosphatidylinositol 3-kinase p110δ specific inhibitor idelalisib has recently been reported to induce complete clinical remission in a stage IV MCC patient. Here we assessed the expression of p110δ in primary MCC and MCC cell lines including its functionality.
Immunofluorescence microscopy revealed a specific cytoplasmic p110δ 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 p110α 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 p110δ is expressed in the majority of MCCs and cell lines its inhibition by idelalisib alone does not suffice to effectively affect MCC cells viability.
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