کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8476879 1550861 2015 33 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Breast cancer cells: Modulation by melatonin and the ubiquitin-proteasome system - A review
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Breast cancer cells: Modulation by melatonin and the ubiquitin-proteasome system - A review
چکیده انگلیسی
Melatonin inhibits human breast cancer cells stimulated with estrogen. This antiproliferative action depends on the presence of the estrogen receptor alpha (ERα) in the human MCF-7 cell line and is strictly dose-dependent. Since researchers concerned with melatonin and breast cancer have not considered the relevance of the ubiquitin-proteasome system to this research in this review we do so. The fact that the first breast cancer susceptibility gene to be identified, Brca1, functions as a ubiquitin ligase indicates that the ubiquitin-proteasome system has a role in regulating susceptibility to breast cancer. While mutations of this gene increase the incidence of breast cancer, the wild type gene suppresses estrogen-dependent transcriptional events relying on the estrogen receptor ERα. Three other ubiquitin ligases, SCFSkp2, E6AP and APC, interact directly with ERα at the ERE and AP-1 promoters of ERα target genes. Melatonin, like proteasome inhibitors, decreases estrogen-induced gene transcription. Indeed, it has been reported that melatonin specifically inhibits estrogen-induced transcription mediated by ERα at the ERE and AP1 gene promoters. Herein, we present a model in which the inhibitory action of melatonin on MCF-7 cells is mediated, directly or indirectly, by the ubiquitin-proteasome system. In this model ERα, apoptotic proteins, and cell cycle proteins, all influenced by melatonin, are substrates of key ubiquitin ligases including SCFSkp2, E6AP, and SCFB−TrCP. Since dysfunction of the ubiquitin-proteasome system is a risk factor for breast cancer, this model provides a context in which to test the clinical potential, and limitations, of melatonin and proteasome inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 417, 5 December 2015, Pages 1-9
نویسندگان
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