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| Content Provider | Springer Nature Link |
|---|---|
| Author | Fraser, Alison V. Goodwin, Andrew C. Hacker Prietz, Amy Sugar, Elizabeth Woster, Patrick M. Casero, Robert A. |
| Copyright Year | 2011 |
| Abstract | Ornithine decarboxylase antizyme 1 (AZ1) is a major regulatory protein responsible for the regulation and degradation of ornithine decarboxylase (ODC). To better understand the role of AZ1 in polyamine metabolism and in modulating the response to anticancer polyamine analogues, a small interfering RNA strategy was used to create a series of stable clones in human H157 non-small cell lung cancer cells that expressed less than 5–10% of basal AZ1 levels. Antizyme 1 knockdown clones accumulated greater amounts of the polyamine analogue N 1,N 11-bis(ethyl)norspermine (BENSpm) and were more sensitive to analogue treatment. The possibility of a loss of polyamine uptake regulation in the knockdown clones was confirmed by polyamine uptake analysis. These results are consistent with the hypothesis that AZ1 knockdown leads to dysregulation of polyamine uptake, resulting in increased analogue accumulation and toxicity. Importantly, there appears to be little difference between AZ1 knockdown cells and cells with normal levels of AZ1 with respect to ODC regulation, suggesting that another regulatory protein, potentially AZ2, compensates for the loss of AZ1. The results of these studies are important for the understanding of both the regulation of polyamine homeostasis and in understanding the factors that regulate tumor cell sensitivity to the anti-tumor polyamine analogues. |
| Starting Page | 529 |
| Ending Page | 538 |
| Page Count | 10 |
| File Format | |
| ISSN | 09394451 |
| Journal | Amino Acids |
| Volume Number | 42 |
| Issue Number | 2-3 |
| e-ISSN | 14382199 |
| Language | English |
| Publisher | Springer Vienna |
| Publisher Date | 2011-08-04 |
| Publisher Place | Vienna |
| Access Restriction | Subscribed |
| Subject Keyword | Antizyme Ornithine decarboxylase Polyamines Spermine BENSpm Neurobiology Life Sciences Biochemistry Proteomics Biochemical Engineering Analytical Chemistry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Organic Chemistry Biochemistry Clinical Biochemistry |
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