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Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41...

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Autores principales: Hafner, Christian, Houben, Roland, Baeurle, Anne, Ritter, Cathrin, Schrama, David, Landthaler, Michael, Becker, Juergen C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281946/
https://www.ncbi.nlm.nih.gov/pubmed/22363598
http://dx.doi.org/10.1371/journal.pone.0031255
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author Hafner, Christian
Houben, Roland
Baeurle, Anne
Ritter, Cathrin
Schrama, David
Landthaler, Michael
Becker, Juergen C.
author_facet Hafner, Christian
Houben, Roland
Baeurle, Anne
Ritter, Cathrin
Schrama, David
Landthaler, Michael
Becker, Juergen C.
author_sort Hafner, Christian
collection PubMed
description Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients.
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spelling pubmed-32819462012-02-23 Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma Hafner, Christian Houben, Roland Baeurle, Anne Ritter, Cathrin Schrama, David Landthaler, Michael Becker, Juergen C. PLoS One Research Article Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients. Public Library of Science 2012-02-17 /pmc/articles/PMC3281946/ /pubmed/22363598 http://dx.doi.org/10.1371/journal.pone.0031255 Text en Hafner et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hafner, Christian
Houben, Roland
Baeurle, Anne
Ritter, Cathrin
Schrama, David
Landthaler, Michael
Becker, Juergen C.
Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma
title Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma
title_full Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma
title_fullStr Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma
title_full_unstemmed Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma
title_short Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma
title_sort activation of the pi3k/akt pathway in merkel cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281946/
https://www.ncbi.nlm.nih.gov/pubmed/22363598
http://dx.doi.org/10.1371/journal.pone.0031255
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