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Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma

Please always quote using this URN: urn:nbn:de:bvb:20-opus-131398
  • 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,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.show moreshow less

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Metadaten
Author: Christian Hafner, Roland Houben, Anne Baeurle, Cathrin Ritter, David Schrama, Michael Landthaler, Jürgen C. Becker
URN:urn:nbn:de:bvb:20-opus-131398
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Language:English
Parent Title (English):PLoS One
Year of Completion:2012
Volume:7
Issue:2
Pagenumber:e31255
Source:PLoS ONE 7(2): e31255. doi:10.1371/journal.pone.0031255
DOI:https://doi.org/10.1371/journal.pone.0031255
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:PIK3CA mutations; T-antigen; akt; cancer; expression; melanoma; polymavirus; rare; squamous cell; tumors
Release Date:2016/12/13
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung