Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: Sporadic sacral chordoma tumors and cell lines examined commonly displayed hyperactivated Akt and mTORC1 signaling. Strikingly, expression of PTEN, a negative regulator of mTORC1 signaling, was not detected or significantly reduced in chordoma-derived cell lines and primary tumors. Furthermore, rapamycin inhibited mTORC1 activation and suppressed proliferation of chordoma-derived cell line. CONCLUSIONS: Our results suggest that loss of PTEN as well as other genetic alterations that result in constitutive activation of Akt/ mTORC1 signaling may contribute to the development of sporadic chordomas. More importantly, a combination of Akt and mTORC1 inhibition may provide clinical benefits to chordoma patients.
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Authors | Sangyeul Han, Carolyn Polizzano, Gunnlaugur P Nielsen, Francis J Hornicek, Andrew E Rosenberg, Vijaya Ramesh |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 15
Issue 6
Pg. 1940-6
(Mar 15 2009)
ISSN: 1078-0432 [Print] United States |
PMID | 19276265
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Multiprotein Complexes
- Proteins
- Transcription Factors
- Tuberous Sclerosis Complex 2 Protein
- Tumor Suppressor Proteins
- Mechanistic Target of Rapamycin Complex 1
- Proto-Oncogene Proteins c-akt
- TOR Serine-Threonine Kinases
- PTEN Phosphohydrolase
- PTEN protein, human
- Sirolimus
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Topics |
- Cell Proliferation
(drug effects)
- Chordoma
(etiology, metabolism)
- Humans
- Mechanistic Target of Rapamycin Complex 1
- Multiprotein Complexes
- PTEN Phosphohydrolase
(analysis, physiology)
- Proteins
- Proto-Oncogene Proteins c-akt
(physiology)
- Signal Transduction
(drug effects, physiology)
- Sirolimus
(pharmacology)
- TOR Serine-Threonine Kinases
- Transcription Factors
(physiology)
- Tuberous Sclerosis Complex 2 Protein
- Tumor Suppressor Proteins
(physiology)
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