Addition of a histone deacetylase inhibitor redirects tamoxifen-treated breast cancer cells into apoptosis, which is opposed by the induction of autophagy.
Addition of a histone deacetylase inhibitor redirects tamoxifen-treated breast cancer cells into apoptosis, which is opposed by the induction of autophagy.
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DOI：
10.1007/s10549-011-1364-y
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发表时间：
2011-11
影响因子：
3.8
通讯作者：
Muenster, Pamela N.
中科院分区：
文献类型：
--
作者：
Thomas, Scott;Thurn, Kenneth T.;Bicaku, Elona;Marchion, Douglas C.;Muenster, Pamela N.
Modulation of estrogen signaling is one of the most successful modalities for the treatment of estrogen receptor (ER)-positive breast cancer, yet de novo and acquired resistance are frequent. Recent data suggests that the induction of autophagy may play a considerable role in promoting tumor cell survival and resistance to anti-estrogen therapy. Hence, bypassing autophagy may offer a novel strategy to enhance the anti-tumor efficacy of anti-estrogens. Histone deacetylases (HDAC) are involved in the regulation of steroid hormone receptor mediated cell signaling and their inhibition potentiates the anti-tumor effects of anti-estrogens. However, the mechanism underlying this anti-tumor activity is poorly understood. In this report, we show that the addition of an HDAC inhibitor redirects the response of ER-positive breast cancer cells when treated with tamoxifen from growth arrest to apoptotic cell death. This redirection requires functional ER signaling and is mediated by a depletion of Bcl-2 and an induction of Bax and Bak, manifesting in cytochrome C release and PARP cleavage. With combined treatment, a subpopulation of cells are refractory to apoptosis and exhibit a strong induction of autophagy. Inhibition of autophagy in these cells, using siRNA directed against Beclin-1 or treatment with chloroquine, further promotes the induction of apoptosis. Thus, supporting prior reports that autophagy acts as a survival mechanism, our findings demonstrate that HDAC and autophagy inhibition directs autophagy-protected cells into apoptotic cell death, which may impair development of tamoxifen resistance.
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影响因子：
3.8
作者：
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通讯作者：
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影响因子：
45.3
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11.2
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Bicaku, Elona;Marchion, Douglas C.;Munster, Pamela N.
通讯作者：
Munster, Pamela N.
影响因子：
12.4
作者：
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