PMID: 24339738Dec 18, 2013Paper

Estrogen receptor β isoform 5 confers sensitivity of breast cancer cell lines to chemotherapeutic agent-induced apoptosis through interaction with Bcl2L12

Neoplasia : an International Journal for Oncology Research
Ming-Tsung LeeYuet-Kin Leung

Abstract

Alternative splicing of estrogen receptor β (ERβ) yields five isoforms, but their functions remain elusive. ERβ isoform 5 (ERβ5) has been positively correlated with better prognosis and longer survival of patients with breast cancer (BCa) in various clinical studies. In this study, we investigated the inhibitory role of ERβ5 in BCa cells. Although ERβ5 does not reduce proliferation of BCa cell lines MCF-7 and MDA-MB-231, its ectopic expression significantly decreases their survival by sensitizing them to doxorubicin- or cisplatin-induced apoptosis through the intrinsic apoptotic pathway. Moreover, we discovered Bcl2L12, which belongs to the Bcl-2 family regulating apoptosis, to be a specific interacting partner of ERβ5, but not ERβ1 or ERα, in an estradiol-independent manner. Knockdown of Bcl2L12 enhanced doxorubicin- or cisplatin-induced apoptosis, and this process was further promoted by ectopic expression of ERβ5. Whereas Bcl2L12 was previously shown to inhibit apoptosis through binding to caspase 7, such interaction is reduced in the presence of ERβ5, suggesting a mechanism by which ERβ5 sensitizes cells to apoptosis. In conclusion, ERβ5 interacts with Bcl2L12 and functions in a novel estrogen-independent molecular pathway ...Continue Reading

Citations

Aug 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Göknil Pelin CoşkunŞ Güniz Küçükgüzel
Sep 30, 2017·International Journal of Cancer. Journal International Du Cancer·Bindu ThapaHasan Uludağ
Aug 28, 2015·International Journal of Molecular Medicine·Lirui ZhangHuilian Hou
Sep 19, 2020·Biomarker Research·Yujing Zhou, Xingdang Liu
Oct 6, 2017·Genes·Nancy Martínez-MontielRebeca D Martínez-Contreras
Nov 5, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karin ElebroHelena Jernström
Nov 10, 2017·Molecular Cancer Research : MCR·Fotis NikolosJan-Åke Gustafsson
Apr 18, 2018·Cancer Research·Jinyou LiuRatna K Vadlamudi

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