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| Content Provider | PubMed Central |
|---|---|
| Author | Shukla, Sanjeev Shukla, Meenakshi Maclennan, Gregory T. Fu, Pingfu Gupta, Sanjay |
| Abstract | Forkhead box transcription factor FOXO3A is an important regulator of cellular function, is thought to act as a tumor suppressor. We studied whether alterations in FOXO3A activity occur in prostate tumorigenesis. Our studies demonstrate that FOXO3A activity is negatively regulated by Akt/PKB through posttranslational modifications. In prostate cancer cells, Akt activation causes increased accumulation of FOXO3A and its binding chaperone protein 14-3-3 in the cytosol. Higher levels of FOXO3A in the cytosol correlated with phosphorylation at Ser253, which accounted for its nuclear exclusion. Dominant negative Akt approach in PC-3 cells increased FOXO3A accumulation in the nucleus, causing upregulation of the downstream target, MnSOD. Conversely, stable DU145-Akt over-expressing cells exhibited decreased FOXO3A levels in the nucleus. Similar findings were noted in prostate tumor specimens, in which marked cytoplasmic accumulation of FOXO3A and 14-3-3 in prostate tumors was observed with increasing Gleason grade, in contrast to exclusively nuclear accumulation in benign prostate cells. These findings correlate with decreased FOXO3A DNA binding activity along with down modulation of FOXO3A transcriptional activity with increasing tumor grade. Our findings demonstrate that tumor associated alterations and redistribution of FOXO3A are frequent events in the etiology of prostate cancer. |
| Starting Page | 1613 |
| File Format | |
| ISSN | 17912423 |
| e-ISSN | 17912423 |
| Journal | International journal of oncology |
| Issue Number | 6 |
| Volume Number | 34 |
| Language | English |
| Publisher Date | 2009-06-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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