Ettl, Tobias and Viale-Bouroncle, Sandra and Hautmann, Matthias G. and Gosau, Martin and Koelbl, Oliver and Reichert, Torsten E. and Morsczeck, Christian (2015) AKT and MET signalling mediates antiapoptotic radioresistance in head neck cancer cell lines. ORAL ONCOLOGY, 51 (2). pp. 158-163. ISSN 1368-8375, 1879-0593
Full text not available from this repository. (Request a copy)Abstract
Objectives: Induction of apoptosis is a major mechanism of radiosensitivity in different types of cancer. In contrast, EGFR/PI3K/AKT signalling and recently the presence of so-called cancer stem cells are discussed as reasons for radioresistance. Materials and methods: The study investigates mechanisms of apoptosis, key oncogenes of the PI3K/AKT pathway and the presence of cancer cells with stem cell properties during irradiation in two cell lines (PCI-9A, and PCI-15) of head and neck squamous cell carcinoma. WST-1-tests, qRT-PCR, western blots and FACS analysis were performed for analysis. Results: The two cell lines presented different degrees of cell death upon irradiation. The radiosensitive cell line PCI-9A showed increased apoptosis after irradiation measured by expressed cleaved caspases 3 and 7 while the radioresistant cell line PCI-15 upregulated antiapoptotic Survivin and BCL2A1 mRNA. Besides, increased PI3K/AKT-and ERK1/2-signalling was associated with radioresistance accompanied by loss of PTEN function through phosphorylation on S380. Blockade of pAKT increased radiation-induced cell death, and moreover, led to an upregulation of pMET in the radioresistant cell line. The percentage of ALDH-positive tumour cells was markedly decreased after irradiation in the radiosensitive cell line. Conclusions: Functional apoptosis is mandatory for sensitivity to irradiation in head neck cancer cells. Upregulation of the AKT-pathway seems to be one reason for poor radioresponse. Activated MET may also predict radioresistance, possibly through ERK1/2 signalling. Moreover MET may indicate the presence of cancer stem cells facilitating radioresistance as shown by increased ALDH expression. (C) 2014 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LOCALLY ADVANCED HEAD; STEM-LIKE CELLS; CARCINOMA-CELLS; BREAST-CANCER; THERAPEUTIC TARGET; RADIATION-THERAPY; DOWN-REGULATION; PLUS CETUXIMAB; LUNG-CANCER; C-MYC; Head neck cancer; Irradiation; Apoptosis; Stem cells; AKT; MET; ALDH |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Lehrstuhl für Strahlentherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jul 2019 08:57 |
| Last Modified: | 25 Jul 2019 08:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6064 |
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