The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells.
Over-expression of the proto-oncogene Akt/PKB has been demonstrated in some neuroendocrine tumor models. Akt may activate downstream proteins such as mTOR and p70S6K, inducing tumor proliferation. The rapamycin-derivative RAD001, everolimus, interacts with this pathway by antagonizing mTOR, but its...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2010
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| _version_ | 1797098781572857856 |
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| author | Grozinsky-Glasberg, S Rubinfeld, H Nordenberg, Y Gorshtein, A Praiss, M Kendler, E Feinmesser, R Grossman, AB Shimon, I |
| author_facet | Grozinsky-Glasberg, S Rubinfeld, H Nordenberg, Y Gorshtein, A Praiss, M Kendler, E Feinmesser, R Grossman, AB Shimon, I |
| author_sort | Grozinsky-Glasberg, S |
| collection | OXFORD |
| description | Over-expression of the proto-oncogene Akt/PKB has been demonstrated in some neuroendocrine tumor models. Akt may activate downstream proteins such as mTOR and p70S6K, inducing tumor proliferation. The rapamycin-derivative RAD001, everolimus, interacts with this pathway by antagonizing mTOR, but its effects on neuroendocrine tumors are largely unknown. We explored the mechanism of action of RAD001 on cell proliferation, hormonal secretion and on Akt/mTOR/p70S6K pathway activation, in a human medullary thyroid carcinoma (MTC) cell-line (TT) and in cells derived from human MTCs. Treatment with RAD001 significantly inhibited cell viability in a dose- and time-dependent fashion, and diminished phosphorylation of Akt downstream targets, mTOR and p70S6K, in both TT cell-line and cultured human MTCs. Akt phosphorylation was not affected by RAD001. RAD001 induced cell-cycle arrest in the G(0)/G(1) phase in TT cells, but had no effect on apoptosis. Moreover, RAD001 did not affect calcitonin and carcinoembryonic antigen secretion in TT cells and in human MTCs. RAD001 seems to have potent anti-proliferative effect in human MTC cells, which suggest that clinical trials of this agent are of considerable interest. |
| first_indexed | 2024-03-07T05:14:34Z |
| format | Journal article |
| id | oxford-uuid:dcba650e-d950-4056-9a5e-9fd989b98c8d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:14:34Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:dcba650e-d950-4056-9a5e-9fd989b98c8d2022-03-27T09:19:42ZThe rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dcba650e-d950-4056-9a5e-9fd989b98c8dEnglishSymplectic Elements at Oxford2010Grozinsky-Glasberg, SRubinfeld, HNordenberg, YGorshtein, APraiss, MKendler, EFeinmesser, RGrossman, ABShimon, IOver-expression of the proto-oncogene Akt/PKB has been demonstrated in some neuroendocrine tumor models. Akt may activate downstream proteins such as mTOR and p70S6K, inducing tumor proliferation. The rapamycin-derivative RAD001, everolimus, interacts with this pathway by antagonizing mTOR, but its effects on neuroendocrine tumors are largely unknown. We explored the mechanism of action of RAD001 on cell proliferation, hormonal secretion and on Akt/mTOR/p70S6K pathway activation, in a human medullary thyroid carcinoma (MTC) cell-line (TT) and in cells derived from human MTCs. Treatment with RAD001 significantly inhibited cell viability in a dose- and time-dependent fashion, and diminished phosphorylation of Akt downstream targets, mTOR and p70S6K, in both TT cell-line and cultured human MTCs. Akt phosphorylation was not affected by RAD001. RAD001 induced cell-cycle arrest in the G(0)/G(1) phase in TT cells, but had no effect on apoptosis. Moreover, RAD001 did not affect calcitonin and carcinoembryonic antigen secretion in TT cells and in human MTCs. RAD001 seems to have potent anti-proliferative effect in human MTC cells, which suggest that clinical trials of this agent are of considerable interest. |
| spellingShingle | Grozinsky-Glasberg, S Rubinfeld, H Nordenberg, Y Gorshtein, A Praiss, M Kendler, E Feinmesser, R Grossman, AB Shimon, I The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. |
| title | The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. |
| title_full | The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. |
| title_fullStr | The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. |
| title_full_unstemmed | The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. |
| title_short | The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. |
| title_sort | rapamycin derivative rad001 everolimus inhibits cell viability and interacts with the akt mtor p70s6k pathway in human medullary thyroid carcinoma cells |
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