Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Hafner, C; Houben, R; Baeurle, A; Ritter, C; Schrama, D; Landthaler, M; Becker, JC.
Activation of the PI3K/AKT pathway in Merkel cell carcinoma.
PLoS One. 2012; 7(2):e31255-e31255
Doi: 10.1371/journal.pone.0031255
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Becker Jürgen Christian
- Ritter Cathrin
- Schrama David
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, Polyomavirus Transforming - metabolism
- Base Sequence -
- Carcinoma, Basal Cell - enzymology Carcinoma, Basal Cell - pathology
- Carcinoma, Merkel Cell - enzymology Carcinoma, Merkel Cell - genetics Carcinoma, Merkel Cell - pathology
- Cell Line, Tumor -
- Chromones - pharmacology
- DNA Mutational Analysis -
- Enzyme Activation - drug effects
- Humans -
- Molecular Sequence Data -
- Morpholines - pharmacology
- Mutation - genetics
- Phosphatidylinositol 3-Kinases - antagonists and inhibitors Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism
- Phosphorylation - drug effects
- Phosphothreonine - metabolism
- Proto-Oncogene Proteins c-akt - metabolism
- Signal Transduction - drug effects
- Skin Neoplasms - enzymology Skin Neoplasms - genetics Skin Neoplasms - pathology