Phosphatidylinositol 3-kinase p110δ expression in Merkel cell carcinoma

Emil Chteinberg, Dorit Rennspiess, Ryan Sambo, S. Tauchmann, N. W. J. Kelleners-Smeets, Veronique Winnepenninckx, Ernst Speel, Anna Kordelia Kurz, Martin Zenke, Axel zur Hausen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)29565-29573
JournalOncotarget
Volume9
Issue number51
DOIs
Publication statusPublished - 2018

Cite this

Chteinberg, Emil ; Rennspiess, Dorit ; Sambo, Ryan ; Tauchmann, S. ; Kelleners-Smeets, N. W. J. ; Winnepenninckx, Veronique ; Speel, Ernst ; Kurz, Anna Kordelia ; Zenke, Martin ; zur Hausen, Axel. / Phosphatidylinositol 3-kinase p110δ expression in Merkel cell carcinoma. In: Oncotarget. 2018 ; Vol. 9, No. 51. pp. 29565-29573.
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title = "Phosphatidylinositol 3-kinase p110δ expression in Merkel cell carcinoma",
abstract = "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.",
author = "Emil Chteinberg and Dorit Rennspiess and Ryan Sambo and S. Tauchmann and Kelleners-Smeets, {N. W. J.} and Veronique Winnepenninckx and Ernst Speel and Kurz, {Anna Kordelia} and Martin Zenke and {zur Hausen}, Axel",
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Phosphatidylinositol 3-kinase p110δ expression in Merkel cell carcinoma. / Chteinberg, Emil; Rennspiess, Dorit; Sambo, Ryan; Tauchmann, S.; Kelleners-Smeets, N. W. J. ; Winnepenninckx, Veronique; Speel, Ernst; Kurz, Anna Kordelia; Zenke, Martin; zur Hausen, Axel.

In: Oncotarget, Vol. 9, No. 51, 2018, p. 29565-29573.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Chteinberg, Emil

AU - Rennspiess, Dorit

AU - Sambo, Ryan

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AU - Kelleners-Smeets, N. W. J.

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AU - zur Hausen, Axel

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AB - 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.

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