期刊
STEROIDS
卷 75, 期 8-9, 页码 560-564出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.steroids.2010.01.013
关键词
ER alpha; Src; PI3K; FAK; PRMT1; Breast cancer
Estrogen receptor a (ER alpha) is a member of a large conserved superfamily of steroid hormone nuclear receptors which regulates many physiological pathways by acting as a ligand-dependent transcription factor. Evidence is emerging that estrogens also induce rapid signaling to the downstream kinase cascades; however the mechanisms underlying this nongenomic function remain poorly understood. We have recently shown that ER alpha is methylated specifically by the arginine methyltransferase PRMT1 at arginine 260 in the DNA-binding domain of the receptor. This methylation event is required for mediating the extra-nuclear function of the receptor which would thereby interact with Src/FAK and p85 and propagate the signal to downstream transduction cascades that orchestrate cell proliferation and survival. Of particular interest, a possible role of methylated ER alpha in mammary tumorigenesis is also evident by the fact that, as demonstrated by immunohistochemical studies on a cohort of breast cancer patients, ER alpha is methylated in normal epithelial breast cells and is hypermethylated in a subset of breast cancers. Hypermethylation of ER alpha in breast cancer might cause hyperactivation of cellular kinase signaling, notably of Akt, described as a selective survival advantage for primary tumor cells even in the presence of anti-estrogens. A detailed understanding of the molecular mechanisms that control estrogen signaling in breast cancer is a crucial step in identifying new effective therapies. (C) 2010 Elsevier Inc. All rights reserved.
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