| PIM1-Activated PRAS40 Regulates Radioresistance in Non-small Cell Lung Cancer Cells through Interplay with FOXO3a, 14-3-3 and Protein Phosphatases. | |
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MedLine Citation:
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PMID: 21910584 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Resistance of cancer cells to ionizing radiation plays an important role in the clinical setting of lung cancer treatment. To date, however, the exact molecular mechanism of radiosensitivity has not been well explained. In this study, we compared radioresistance in two types of non-small cell lung cancer (NSCLC) cells, NCI-H460 and A549, and investigated the signaling pathways that confer radioresistance. In radioresistant cells, exposure to radiation led to overexpression of PIM1 and reduction of protein phosphatases (PP2A and PP5), which induced translocation of PIM1 into the nucleus. Increased nuclear PIM1 phosphorylated PRAS40. Consequently, pPRAS40 made a trimeric complex with 14-3-3 and AKT-activated pFOXO3a, which then moved rapidly to the cytoplasm. Cytoplasmic retention of FOXO3a was associated with downregulation of proapoptotic genes and possibly radioresistance. On the other hand, no suppressive effect of radiation on protein phosphatases was detected and, concomitantly, protein phosphatases downregulated PIM1 in radiosensitive cells. In this setting, PIM1-activated pPRAS40, AKT-activated pFOXO3a, and their complex formation with 14-3-3 could be key regulators of the radiation-induced radioresistance in NSCLC cells. |
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Authors:
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Wanyeon Kim; Hyesook Youn; Ki Moon Seong; Hee Jung Yang; Young Ju Yun; Taewoo Kwon; Young Ha Kim; Ji Young Lee; Young-Woo Jin; Buhyun Youn |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-12 |
Journal Detail:
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Title: Radiation research Volume: - ISSN: 1938-5404 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0401245 Medline TA: Radiat Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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a College of Natural Sciences, Department of Biological Sciences, Pusan National University, Busan, South Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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