Enhanced resistance to tamoxifen by the c-ABL proto-oncogene in breast cancer.
Neoplasia
; 12(3): 214-23, 2010 Mar.
Article
en En
| MEDLINE
| ID: mdl-20234815
ABSTRACT
Targeting the estrogen receptor is an important strategy in breast cancer therapy. However, although inhibiting estrogen receptor function with specific estrogen receptor modulators can achieve a primary response in cancer patients, intrinsic or subsequently acquired resistance to the therapy remains a major obstacle in the clinic. Thus, it is critical to gain a more thorough understanding of how estrogen receptor functions are regulated in breast cancer.Here, we demonstrate that the non-receptor tyrosine kinase c-ABL is a functional partner of the estrogen receptor, as expression of c-ABL sustained transcriptional activity of the estrogen receptor. More importantly, inhibition of c-ABL resulted in sensitization to treatment by tamoxifen (TAM) in estrogen receptor-positive breast cancer cells, as manifested by inhibition of cell survival and suppression of anchorage-independent growth. We found that c-ABL interacts with estrogen receptor in breast cancer cells and that expression of c-ABL is a frequent event in primary breast cancer tumor tissues. In estrogen receptor-positive tumors, the expression of c-ABL significantly correlated with disease progression and metastasis. This study shows that c-ABL regulates the cellular response to TAM through functional interaction with the estrogen receptor, which suggests c-ABL as a therapeutic target and a prognostic tumor marker for breast cancer.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tamoxifeno
/
Neoplasias de la Mama
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Genes abl
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Resistencia a Antineoplásicos
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Antineoplásicos Hormonales
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Receptor alfa de Estrógeno
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Neoplasia
Asunto de la revista:
NEOPLASIAS
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos