Abstract |
The phosphatidylinositol 3' kinase (PI3K)/ phosphatase and tensin homologue deleted on chromosome ten/Akt pathway, which is a critical regulator of cell proliferation and survival, is mutated or activated in a wide variety of cancers. Akt appears to be a key central node in this pathway and thus is an attractive target for targeted molecular therapy. We demonstrated that Akt is highly phosphorylated in thyroid cancer cell lines and human thyroid cancer specimens, and hypothesised that KP372-1, an Akt inhibitor, would block signalling through the PI3K pathway and inhibit cell proliferation while inducing apoptosis of thyroid cancer cells. KP372-1 blocked signalling downstream of Akt in thyroid tumour cells, leading to inhibition of cell proliferation and increased apoptosis. As thyroid cancer consistently expresses phosphorylated Akt and KP372-1 effectively blocks Akt signalling, further preclinical evaluation of this compound for treatment of thyroid cancer is warranted.
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Authors | M Mandal, S Kim, M N Younes, S A Jasser, A K El-Naggar, G B Mills, J N Myers |
Journal | British journal of cancer
(Br J Cancer)
Vol. 92
Issue 10
Pg. 1899-905
(May 23 2005)
ISSN: 0007-0920 [Print] England |
PMID | 15870708
(Publication Type: Journal Article, Retracted Publication)
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Chemical References |
- Heterocyclic Compounds, 4 or More Rings
- KP372-1
- Proto-Oncogene Proteins
- Tetrazoles
- AKT1 protein, human
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins c-akt
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Topics |
- Apoptosis
(drug effects)
- Cell Proliferation
(drug effects)
- DNA Damage
- Heterocyclic Compounds, 4 or More Rings
(pharmacology)
- Humans
- Phosphorylation
- Protein Serine-Threonine Kinases
(antagonists & inhibitors, metabolism, pharmacology)
- Proto-Oncogene Proteins
(antagonists & inhibitors, metabolism, pharmacology)
- Proto-Oncogene Proteins c-akt
- Signal Transduction
- Tetrazoles
(pharmacology)
- Thyroid Neoplasms
(pathology)
- Tumor Cells, Cultured
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