当前位置:
X-MOL 学术
›
Cell. Oncol.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Endocrine resistant breast cancer cells with loss of ERα expression retain proliferative ability by reducing caspase7-mediated HDAC3 cleavage.
Cellular Oncology ( IF 4.9 ) Pub Date : 2019-11-07 , DOI: 10.1007/s13402-019-00439-x Shiyi Yu 1 , Xue Gong 1 , Zhifang Ma 1 , Meng Zhang 1 , Ling Huang 1 , Jun Zhang 1 , Shuang Zhao 2 , Tao Zhu 3 , Zhenghong Yu 2 , Liming Chen 1
中文翻译:
ERα表达缺失的内分泌抗性乳腺癌细胞通过减少caspase7介导的HDAC3裂解而保留了增殖能力。
更新日期:2019-11-07
Cellular Oncology ( IF 4.9 ) Pub Date : 2019-11-07 , DOI: 10.1007/s13402-019-00439-x Shiyi Yu 1 , Xue Gong 1 , Zhifang Ma 1 , Meng Zhang 1 , Ling Huang 1 , Jun Zhang 1 , Shuang Zhao 2 , Tao Zhu 3 , Zhenghong Yu 2 , Liming Chen 1
Affiliation
Purpose
Endocrine therapy is the most commonly used approach for the treatment of estrogen receptor (ERα)-positive breast cancer. The cure rate of patients with ERα-positive breast cancer is, however, limited due to the occurrence of endocrine resistance. Loss of ERα is one major mechanism for the occurrence of endocrine resistance. Recent studies have shown that pan-HDAC inhibitors may be effective in reversing endocrine resistance. However, the molecular mechanism underlying this reversal has remained largely unknown. Here we aimed to unravel this mechanism.Methods
Endocrine resistant breast cancer cell lines were established through exposure to tamoxifen. mRNA expression was assessed by qRT-PCR and protein expression by Western blotting. The effect of HDAC3 inhibition on the viability of endocrine resistant breast cancer cells was evaluated using CCK-8 and colony forming assays. Immunohistochemistry was used to detect protein expression in primary breast cancer tissues.Results
We found that in endocrine resistant breast cancer cells loss of ERα led to HDAC3 stabilization via decreased ERα-mediated caspase7 expression, resulting in reduced caspase7-mediated HDAC3 cleavage. We also found that the ERα-caspase7-HDAC3 axis determined the global H3K9 and H4K16 acetylation status, which was positively correlated with ERα expression. Finally, we found that inhibition of HDAC3 significantly decreased the viability of endocrine resistant breast cancer cells exhibiting ERα deficiency. The ERα-caspase7-HDAC3 axis was subsequently verified in primary endocrine resistant breast cancer samples.Conclusions
From our data we conclude that the ERα-caspase7-HDAC3 axis may play a role in promoting the proliferation of endocrine resistant breast cancer cells. HDAC3 may serve as a therapeutic target for (a subset of) endocrine resistant breast cancers exhibiting ERα loss.中文翻译:
ERα表达缺失的内分泌抗性乳腺癌细胞通过减少caspase7介导的HDAC3裂解而保留了增殖能力。