Rapamycin inhibits Akt-mediated oncogenic transformation and tumor growth.
Anticancer Res
; 24(5A): 2697-704, 2004.
Article
em En
| MEDLINE
| ID: mdl-15517874
ABSTRACT
Akt is a serine/threonine kinase that plays a critical role in cell survival and proliferation. Three isoforms of Akt have been identified and have been shown to be up-regulated in human malignancies. We examined the requirement of these pathways for Akt transformation. We generated NIH-3T3 cells over-expressing constitutively active Myr-Akt1 (3T3-Akt1 cells) or Myr-Akt2 (3T3-Akt2 cells). These cells are able to form colonies in soft-agar and 3T3-Akt1 cells formed tumors in SCID mice. Rapamycin efficiently inhibited the activation of the mTOR-p70S6K pathway and the anchorage-independent growth of both 3T3-Akt cells, demonstrating the importance of the mTOR-p70S6K pathway for transformation by Akt1 as well as by Akt2. Moreover, rapamycin dramatically inhibited the tumor formation by 3T3-Akt1 cells in SCID mice. Thus, we demonstrated the importance of mTOR-p70S6 kinase pathway in the transformation by Akt, both in tissue-cultured cells and in animal tumor models. In contrast, neither the MAPK pathway nor the p38 MAPK pathway is required for Akt-dependent transformation of NIH3T3 cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
/
Proteínas Proto-Oncogênicas
/
Proteínas Serina-Treonina Quinases
/
Sirolimo
/
Antibióticos Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos