Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/62635
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Predominance of mTORC1 over mTORC2 in the regulation of proliferation of ovarian cancer cells: Therapeutic implications |
Autor: | Montero, Juan Carlos CSIC ORCID; Chen, Xi CSIC; Ocaña, Alberto; Pandiella, Atanasio CSIC ORCID CVN | Fecha de publicación: | 2012 | Editor: | American Association for Cancer Research | Citación: | Molecular Cancer Therapeutics 11(6): 1342-1352 (2012) | Resumen: | mTOR is a serine/threonine kinase that acts by binding different sets of proteins forming two complexes, termed mTORC1 and mTORC2. mTOR is deregulated in a substantial proportion of ovarian tumors. Despite the use of drugs directed to mTOR in ongoing clinical trials, the functional relevance of the individual mTORC branches in ovarian cancer is not known. Here, we show that mTORC1 and mTORC2 were constitutively active in ovarian cancer cell lines. Knockdown of raptor or rictor, proteins required for the function of mTORC1 or mTORC2, respectively, resulted in profound inhibition of ovarian cancer cell proliferation. The knockdown of raptor had a more important inhibitory effect than the knockdown of rictor, indicating mTORC1 had a predominant role over mTORC2 in the control of ovarian cancer cell proliferation. Rapamycin decreased the proliferation of ovarian cancer cells, and this was accompanied by inhibition of the phosphorylation of S6, a protein used as readout of mTORC1 function. However, rapamycin had only amarginal effect on the phosphorylation status of 4E-BP1, anothermTORC1 substrate. Therefore, mTORC1 probably controls p4E-BP1 along two distinct pathways, one of them sensitive to rapamycin and another insensitive. The dual PI3K/mTOR inhibitor BEZ235 was more efficient than rapamycin in its inhibitory action on ovarian cancer cell proliferation. Biochemically, BEZ235 completely inhibited pS6, p4E-BP1, and pAkt. Our results suggest that broad-spectrum mTOR inhibitors that block mTORC1 and mTORC2 are more desirable for their clinical development in ovarian cancer than agents exclusively targeting one of the mTOR branches. ©2012 AACR. | URI: | http://hdl.handle.net/10261/62635 | DOI: | 10.1158/1535-7163.MCT-11-0723 | Identificadores: | doi: 10.1158/1535-7163.MCT-11-0723 issn: 1535-7163 e-issn: 1538-8514 |
Aparece en las colecciones: | (IBMCC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
46
checked on 15-may-2024
WEB OF SCIENCETM
Citations
44
checked on 19-feb-2024
Page view(s)
340
checked on 20-may-2024
Download(s)
95
checked on 20-may-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.