Tamoxifen regulates cell fate through mitochondrial estrogen receptor beta in breast cancer.
Oncogene
; 32(27): 3274-85, 2013 Jul 04.
Article
en En
| MEDLINE
| ID: mdl-22907432
Tamoxifen (TAM) has both cytostatic and cytotoxic properties for breast cancer. TAM engaged mitochondrial estrogen receptor beta (ERß) as an antagonist in MCF7-BK cells, increasing reactive oxygen species (ROS) concentrations from the mitochondria that were required for cytotoxicity. In part, this derived from TAM downregulating manganese superoxide dismutase (MnSOD) activity by causing the nitrosylation of tyrosine 34, thereby increasing ROS. ROS-activated protein kinase C delta and c-jun N-terminal kinases, resulting in the mitochondrial translocation of Bax and cytochrome C release. Interestingly, TAM failed to cause high ROS levels or induce cell death in MCF7-BK-TR cells due to stimulation of MnSOD activity through agonistic effects at mitochondrial ERß. In several mouse xenograft models, lentiviral shRNA-induced knockdown of MnSOD caused tumors that grew in the presence of TAM to undergo substantial apoptosis. Tumor MnSOD and mitochondrial ERß are therefore targets for therapeutic intervention to reverse TAM resistance and enhance a cell death response.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tamoxifeno
/
Neoplasias de la Mama
/
Resistencia a Antineoplásicos
/
Moduladores Selectivos de los Receptores de Estrógeno
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Receptor beta de Estrógeno
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Mitocondrias
Límite:
Animals
/
Female
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Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido