Acquisition of epithelial–mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance

Radioresistance is a major challenge in prostate cancer (CaP) radiotherapy (RT). In this study, we investigated the role and association of epithelial–mesenchymal transition (EMT), cancer stem cells (CSCs) and the PI3K/Akt/mTOR signaling pathway in CaP radioresistance. We developed three novel CaP r...

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Veröffentlicht in:	Cell death & disease 2013-10, Vol.4 (10), p.e875-e875
Hauptverfasser:	Chang, L, Graham, P H, Hao, J, Ni, J, Bucci, J, Cozzi, P J, Kearsley, J H, Li, Y
Format:	Artikel
Sprache:	eng
Schlagworte:	631/67/1059/2326 631/67/589/466 631/67/71 631/80/84/2176 Animals Antibodies Apoptosis - drug effects Apoptosis - radiation effects Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Cell Cycle Checkpoints - drug effects Cell Cycle Checkpoints - radiation effects Cell Line, Tumor Enzyme Activation - drug effects Enzyme Activation - radiation effects Epithelial-Mesenchymal Transition - drug effects Epithelial-Mesenchymal Transition - radiation effects Humans Imidazoles - pharmacology Imidazoles - therapeutic use Immunology Life Sciences Male Models, Biological Neoplasm Invasiveness Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - enzymology Neoplastic Stem Cells - pathology Original original-article Phenotype Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Prostatic Neoplasms - drug therapy Prostatic Neoplasms - enzymology Prostatic Neoplasms - pathology Prostatic Neoplasms - radiotherapy Proto-Oncogene Proteins c-akt - metabolism Quinolines - pharmacology Quinolines - therapeutic use Radiation Tolerance - drug effects Radiation Tolerance - radiation effects Reproducibility of Results Signal Transduction - drug effects Signal Transduction - radiation effects Spheroids, Cellular - drug effects Spheroids, Cellular - pathology Spheroids, Cellular - radiation effects TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - metabolism
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Zusammenfassung:	Radioresistance is a major challenge in prostate cancer (CaP) radiotherapy (RT). In this study, we investigated the role and association of epithelial–mesenchymal transition (EMT), cancer stem cells (CSCs) and the PI3K/Akt/mTOR signaling pathway in CaP radioresistance. We developed three novel CaP radioresistant (RR) cell lines (PC-3RR, DU145RR and LNCaPRR) by radiation treatment and confirmed their radioresistance using a clonogenic survival assay. Compared with untreated CaP-control cells, the CaP-RR cells had increased colony formation, invasion ability and spheroid formation capability ( P
ISSN:	2041-4889 2041-4889
DOI:	10.1038/cddis.2013.407