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Cell Death Differ ; 17(2): 246-54, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19730444

RESUMO

Understanding the consequences of miR-145 reintroduction in human breast cancer (BC) could reveal its tumor-suppressive functions and may disclose new aspects of BC biology. Therefore, we characterized the effects of miR-145 re-expression in BC cell lines by using proliferation and apoptosis assays. As a result, we found that miR-145 exhibited a pro-apoptotic effect, which is dependent on TP53 activation, and that TP53 activation can, in turn, stimulate miR-145 expression, thus establishing a death-promoting loop between miR-145 and TP53. We also found that miR-145 can downregulate estrogen receptor-alpha (ER-alpha) protein expression through direct interaction with two complementary sites within its coding sequence. In conclusion, we described a tumor suppression function of miR-145 in BC cell lines, and we linked miR-145 to TP53 and ER-alpha. Moreover, our findings support a view that miR-145 re-expression therapy could be mainly envisioned in the specific group of patients with ER-alpha-positive and/or TP53 wild-type tumors.


Assuntos
Apoptose/genética , Neoplasias da Mama/genética , Receptor alfa de Estrogênio/metabolismo , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Mama/patologia , Divisão Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Ciclina D1/metabolismo , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Transfecção , Proteína Supressora de Tumor p53/genética
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