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Cell Death Differ ; 17(2): 246-54, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19730444

ABSTRACT

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.


Subject(s)
Apoptosis/genetics , Breast Neoplasms/genetics , Estrogen Receptor alpha/metabolism , MicroRNAs/metabolism , Tumor Suppressor Protein p53/metabolism , Breast Neoplasms/pathology , Cell Division/genetics , Cell Line, Tumor , Cell Survival/genetics , Cyclin D1/metabolism , Estrogen Receptor alpha/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Transfection , Tumor Suppressor Protein p53/genetics
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