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| Content Provider | PubMed Central |
|---|---|
| Author | Kubo, Makoto Kanaya, Noriko Petrossian, Karineh Ye, Jingjing Warden, Charles Liu, Zheng Nishimura, Reiki Osako, Tomofumi Okido, Masayuki Shimada, Kazuo Takahashi, Masato Chu, Peiguo Yuan, Yate-ching Chen, Shiuan |
| Abstract | Aromatase inhibitors (AIs) are important drugs for treating postmenopausal patients with hormone receptor (HR)-positive breast cancer. However, acquired resistance to AI therapies is a significant problem. Our study has revealed that the histone deacetylase inhibitor LBH589 treatment abrogated growth of AI-resistant cells in vitro and in vivo, causing cell cycle G2/M arrest, and induced apoptosis. LBH589 treatment also reduce the levels of NF-κB1 which overexpresses when AI-resistance develops. Analyzing paired tumor specimens from 12 patients, we found that NF-κB1 expression was increased in recurrent AI-resistant tumors as compared to the paired primary tumors before AI treatment. This finding was consistent with up-regulated NF-κB1 expression seen in a collection of well-established AI-resistant cell lines. Furthermore, knockdown of NF-κB1 expression significantly suppressed the proliferation of AI-resistant cells. Treatment of AI-resistant cell lines with LBH589 repressed NF-κB1 mRNA and protein expression. In addition, LBH589 treatment abrogated growth of AI-resistant tumors in mice, and was associated with significantly decreased levels of NF-κB1 in tumors. In all, our findings strongly support further investigation of LBH589 as a novel therapeutic strategy for patients with AI-resistant breast cancer, in part by suppressing the NF-κB1 pathway. |
| Related Links | http://dx.doi.org/10.1007/s10549-012-2332-x |
| Ending Page | 107 |
| Page Count | 15 |
| Starting Page | 93 |
| File Format | |
| ISSN | 01676806 |
| e-ISSN | 15737217 |
| Journal | Breast cancer research and treatment |
| Issue Number | 1 |
| Volume Number | 137 |
| Language | English |
| Publisher Date | 2013-01-01 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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