BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer cells.
PTEN loss and constitutive activation of the PI3K signaling pathway have been associated with advanced androgen-independent prostate cancer. PTEN-deficient prostate cancer C42Luc cells survive in serum-free media and show relative resistance to apoptosis even in the presence of the PI3K inhibitor ZS...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3764099?pdf=render |
| _version_ | 1828874406908133376 |
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| author | Dana Yancey Kyle C Nelson Daniele Baiz Sazzad Hassan Anabel Flores Ashok Pullikuth Yelena Karpova Linara Axanova Victoria Moore Guangchao Sui George Kulik |
| author_facet | Dana Yancey Kyle C Nelson Daniele Baiz Sazzad Hassan Anabel Flores Ashok Pullikuth Yelena Karpova Linara Axanova Victoria Moore Guangchao Sui George Kulik |
| author_sort | Dana Yancey |
| collection | DOAJ |
| description | PTEN loss and constitutive activation of the PI3K signaling pathway have been associated with advanced androgen-independent prostate cancer. PTEN-deficient prostate cancer C42Luc cells survive in serum-free media and show relative resistance to apoptosis even in the presence of the PI3K inhibitor ZSTK474. Yet, when ZSTK474 is combined with the translation inhibitor cycloheximide, C42Luc cells undergo apoptosis within 6 hours. We identified dephosphorylation of BAD (Bcl2-associated death promoter) as a main apoptosis-regulatory molecule downstream from PI3K, and loss of MCL-1 (Myeloid cell leukemia -1) as a major target of cycloheximide. The combination of MCL-1 knockdown and expression of phosphorylation-deficient mutant BAD2SA is sufficient to trigger rapid apoptosis in prostate cancer cells. These results establish the mechanism for the synergistic induction of apoptosis by the combination of a PI3K inhibitor and of a protein synthesis inhibitor in PTEN-deficient prostate cancer cells. |
| first_indexed | 2024-12-13T07:36:39Z |
| format | Article |
| id | doaj.art-c48b7283e0894306b04104a460234899 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T07:36:39Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c48b7283e0894306b04104a4602348992022-12-21T23:55:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7456110.1371/journal.pone.0074561BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer cells.Dana YanceyKyle C NelsonDaniele BaizSazzad HassanAnabel FloresAshok PullikuthYelena KarpovaLinara AxanovaVictoria MooreGuangchao SuiGeorge KulikPTEN loss and constitutive activation of the PI3K signaling pathway have been associated with advanced androgen-independent prostate cancer. PTEN-deficient prostate cancer C42Luc cells survive in serum-free media and show relative resistance to apoptosis even in the presence of the PI3K inhibitor ZSTK474. Yet, when ZSTK474 is combined with the translation inhibitor cycloheximide, C42Luc cells undergo apoptosis within 6 hours. We identified dephosphorylation of BAD (Bcl2-associated death promoter) as a main apoptosis-regulatory molecule downstream from PI3K, and loss of MCL-1 (Myeloid cell leukemia -1) as a major target of cycloheximide. The combination of MCL-1 knockdown and expression of phosphorylation-deficient mutant BAD2SA is sufficient to trigger rapid apoptosis in prostate cancer cells. These results establish the mechanism for the synergistic induction of apoptosis by the combination of a PI3K inhibitor and of a protein synthesis inhibitor in PTEN-deficient prostate cancer cells.http://europepmc.org/articles/PMC3764099?pdf=render |
| spellingShingle | Dana Yancey Kyle C Nelson Daniele Baiz Sazzad Hassan Anabel Flores Ashok Pullikuth Yelena Karpova Linara Axanova Victoria Moore Guangchao Sui George Kulik BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer cells. PLoS ONE |
| title | BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer cells. |
| title_full | BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer cells. |
| title_fullStr | BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer cells. |
| title_full_unstemmed | BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer cells. |
| title_short | BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer cells. |
| title_sort | bad dephosphorylation and decreased expression of mcl 1 induce rapid apoptosis in prostate cancer cells |
| url | http://europepmc.org/articles/PMC3764099?pdf=render |
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