Abstract：
:In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, nongenomic responses. E2 activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds to its receptors, leading to important breast cancer signaling. However, the E2 receptor responsible for SphK1 activation has not yet been identified. Here, we demonstrate in triple-negative breast cancer cells, which lack the canonical ERα66 but express the novel splice variant ERα36, that ERα36 is the receptor responsible for E2-induced activation of SphK1 and formation and secretion of S1P and dihydro-S1P, the ligands for S1PRs. Tamoxifen, the first-line endocrine therapy for breast cancer, is an antagonist of ERα66, but an agonist of ERα36, and, like E2, activates SphK1 and markedly increases secretion of S1P. A major problem with tamoxifen therapy is development of acquired resistance. We found that tamoxifen resistance correlated with increased SphK1 and ERα36 expression in tamoxifen-resistant breast cancer cells, in patient-derived xenografts, and in endocrine-resistant breast cancer patients. Our data also indicate that targeting this ERα36 and SphK1 axis may be a therapeutic option to circumvent endocrine resistance and improve patient outcome.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Maczis MA,Maceyka M,Waters MR,Newton J,Singh M,Rigsby MF,Turner TH,Alzubi MA,Harrell JC,Milstien S,Spiegel Sdoi
10.1194/jlr.M085191subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2297-2307issue
12eissn
0022-2275issn
1539-7262pii
jlr.M085191journal_volume
59pub_type
杂志文章abstract：:The surface behavior of a series of cholesteryl esters was studied in mixtures with a model phospholipid, 1-palmitoyl-2-oleoyl phosphatidylcholine. The cholesteryl esters were representative of the predominant forms occurring naturally and qualitative similarities in their phase behavior permits generalization of thei...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-09-01 00:00:00
abstract：:The demand to study the cellular localization of specific lipids has led to recent advances in lipid probes and microscopy. Alkyne lipids bear a small, noninterfering tag and can be detected upon click reaction with an azide-coupled reporter. Fluorescent alkyne lipid imaging crucially depends on appropriate azide repo...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D070565
更新日期：2016-10-01 00:00:00
abstract：:NADPH-dependent lipid peroxidation in liver microsomes, as measured by malondialdehyde formation, decreased by 90% when rats were fed a diet containing 16% coconut oil. This reduction occurred within 1 to 3 days after the rats were placed on this highly saturated diet. The decrease in peroxidation activity was associa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:Human high density lipoprotein enriched in free cholesterol was obtained by exposing the lipoprotein to lipid dispersions having a free cholesterol/lecithin molar ratio greater than two. The metabolism of cholesterol was studied in tissue culture cells exposed to normal and cholesterol-enriched lipoproteins. Incubatio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-03-01 00:00:00
abstract：:The content of serum gangliosides was examined in VM and C57BL/6J (B6) mice that contained subcutaneous metastatic (VM) and non-metastatic (CT-2A) brain tumors, respectively. Gas-liquid chromatography (GLC) and high performance thin-layer chromatography (HPTLC) were used to analyze the serum gangliosides. N-glycolylne...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:We investigated, in the present study, the role of reactive oxygen intermediates (ROI) in the control of macrophage lipoprotein lipase (LPL) secretion. Exposure of murine macrophages to increasing concentrations of hydrogen peroxide (H2O2) resulted in enhanced basal LPL production and mRNA levels. The increase of LPL ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:Triglyceride-rich lipoproteins derived from ten normo- and hyperlipidemic apoE-2 homozygotes were analyzed for their composition, beta-VLDL content, and their ability to induce cholesteryl ester storage in macrophages. In six of these probands apoE sequence analysis revealed that the cysteine residues were at position...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-03-01 00:00:00
abstract：:Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compounds is important from both diagnostic and physiological points of view. Here, we present a novel method for the quantification of 11 intact steroid sulfates in human serum by LC-MS/MS. The compounds analyzed in our method,...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D061499
更新日期：2015-09-01 00:00:00
abstract：:Serine palmitoyltransferase (SPT) catalyzes the rate-limiting step of condensation of L-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine (3KDS). Here, we report a HPLC-ESI-MS/MS method to directly quantify 3KDS generated by SPT. With this technique, we were able to detect 3KDS at a level comparable to that of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D078535
更新日期：2018-01-01 00:00:00
abstract：:We have reported the use of a retroviral vector to introduce the low density lipoprotein (LDL) receptor gene into receptor-deficient Watanabe heritable hyperlipidemic (WHHL) rabbit fibroblasts (Miyanohara, A., M. F. Sharkey, D. Steinberg, J. L. Witztum, and T. Friedmann. 1988. Proc. Natl. Acad. Sci. USA. 85: 6538-6542...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:The class B scavenger receptors SR-BI and CD36 exhibit a broad ligand binding specificity. SR-BI is well characterized as a HDL receptor that mediates selective cholesteryl ester uptake from HDL. CD36, a receptor for oxidized LDL, also binds HDL and mediates selective cholesteryl ester uptake, although much less effic...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300417-JLR200
更新日期：2004-04-01 00:00:00
abstract：:Analysis of plasma nonesterified fatty acids (NEFA) by gas-liquid chromatography requires procedures that are both lengthy and cumbersome. A 45-min direct methylation procedure was carried out at 24-29 degrees C on 150 microliter of plasma added with an internal standard in 5.0 ml of methanol-acetyl chloride 50:1 (v/v...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:Cholesterol 7alpha-hydroxylase (CYP7A1) plays a crucial role in cholesterol metabolism and has been implicated in genetic susceptibility to atherosclerosis. Thus, an understanding of its transcriptional regulation is of considerable importance. We evaluated the effect of a common -203A>C polymorphism in the CYP7A1 pro...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800364-JLR200
更新日期：2008-12-01 00:00:00
abstract：:Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to aff...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100254-jlr200
更新日期：2002-07-01 00:00:00
abstract：:An online, two-dimensional (2D) liquid chromatography (LC) quadrupole time-of-flight mass spectrometry (QToF-MS) method was developed for lipid profiling of rat peritoneal surface layers, in which the lipid classes and species could be simultaneously separated in one injection with a significantly increased sensitivit...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D007567
更新日期：2010-09-01 00:00:00
abstract：:HDL cholesterol levels are decreased in Crohn's disease, a tumor necrosis factor-alpha (TNF-alpha)-driven chronic inflammatory condition involving the gastrointestinal tract. ATP-binding cassette transporter A1 (ABCA1), one of several liver X receptor (LXR) target genes, is a cell surface transporter that mediates the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M002410
更新日期：2010-06-01 00:00:00
abstract：:Hepatocytes express on their surfaces more than one class of receptors capable of mediating the internalization of lipoproteins. However, relatively little is known about the binding characteristics of hepatic receptors for various lipoproteins, about the regulation of the receptors, and about the consequences for int...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-12-01 00:00:00
abstract：:Phosphorylcholine-1,2-(14)C and choline-1,2-(14)C-labeled cytidine diphosphate choline are incorporated into lecithin by whole homogenates and particulate fractions of rat retina with optimal incorporation of label by the microsomal fraction. The soluble fraction contains a factor(s) which stimulates incorporation of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1970-11-01 00:00:00
abstract：:The central region of apolipoprotein A-I (apoA-I), spanning residues 143--165, has been implicated in lecithin:cholesterol acyltransferase (LCAT) activation and also in high density lipoprotein (HDL) structural rearrangements. To examine the role of individual amino acids in these functions, we constructed, overexpres...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：:The phase behavior and temperature-dependent molecular motions of three cholesteryl ethers (caproyl, myristyl, oleyl) and a cholesteryl carbonate (oleyl) were characterized. The properties of each ether were qualitatively similar to, but quantitatively different from, those of the corresponding cholesteryl ester. For ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:The relationship between overnight postabsorptive (fasting) respiratory exchange ratio (RER) and plasma FFA concentrations was addressed using data from three separate protocols, each of which involved careful control of the antecedent diet. Protocol 1 examined the relationship between fasting RER and the previous day...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.M900021-JLR200
更新日期：2009-09-01 00:00:00
abstract：:Cerebrosides containing either threo- or erythro-[3-3-H]sphingosine were synthesized by a new procedure. Glucopyranosyl or galactopyranosyl ceramides were converted to their 3-keto derivatives with 2,3-dichloro-5,6-dicyanobenzoquinone and reduced with 3-H-labeled sodium borohydride. The resulting tritiated cerebroside...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-07-01 00:00:00
abstract：:The reversibility and regression of histological and biochemical findings in a mouse model of Gaucher disease (4L/PS-NA) was evaluated using a liver-enriched activator protein promoter control of a tetracycline-controlled transcriptional activation-responsive human acid beta-glucosidase (hGCase) transgenic system. 4L/...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600239-JLR200
更新日期：2006-10-01 00:00:00
abstract：:Lipid peroxidation is a common event in health and is greatly accelerated in pro-inflammatory settings such as hypercholesterolemia. Consequently, oxidation-specific epitopes are generated, which are pro-inflammatory and immunogenic, leading to both adaptive and innate responses. Because innate immune mechanisms use c...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800100-JLR200
更新日期：2009-04-01 00:00:00
abstract：:This study was undertaken to determine the mechanisms that regulate cholesterol synthesis in vivo and to quantitate the relative importance of the liver and extrahepatic tissues as sites for sterol synthesis. Rats were administered [3H]water intravenously and killed 1 hour later. The amount of [3H]water incorporated i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-03-01 00:00:00
abstract：:Rat liver microsomes were incubated with the monofunctional aminoreagent fluorescamine. Although the probe easily penetrated the membranes, two pools of phosphatidylethanolamine (PE) could be detected. The first pool rapidly reacted with the probe and comprised 80% of the total PE. The second pool exhibited a very slo...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-07-01 00:00:00
abstract：:Endothelial lipase (EL) has been shown to be a critical determinant for high density lipoprotein cholesterol levels in vivo; therefore, assays that measure EL activity have become important for the discovery of small molecule inhibitors that specifically target EL. Here, we describe fluorescent Bodipy-labeled substrat...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D600041-JLR200
更新日期：2007-02-01 00:00:00
abstract：:Liver and kidney microsomes have been found to catalyze a rapid decarboxylation of retinoic acid in vitro. The reaction requires NADPH and Fe(2+), and is further stimulated by the presence of pyrophosphate. Thiamine pyrophosphate contained sufficient iron as an impurity to provide strong enhancement of the reaction in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-07-01 00:00:00
abstract：:Based on our previous observation that monoclonal antibody anti-apoD-4E11 reacted with several HDL proteins we studied them further with three questions in mind: i) is there common protein polymorphism in healthy individuals? ii) how many proteins are present and what are their characteristics? iii) are they all apoli...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:Gel-permeation chromatography on Sephadex LH-20, using ethanol as eluent, permits the resolution of neutral hydroxy lipids according to molecular size. The influence of molecular shape, functional groups, chain lengths, and degree of unsaturation, as well as the effect of the eluent on the elution pattern are discusse...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1970-03-01 00:00:00
