Abstract:
:Breast cancer is a heterogeneous disease, and the complexity of breast carcinogenesis is associated with epigenetic modification. There are several major classes of epigenetic enzymes that regulate chromatin activity. This review will focus on the nine mammalian protein arginine methyltransferases (PRMTs) and the dysregulation of PRMT expression and function in breast cancer. This class of enzymes catalyse the mono- and (symmetric and asymmetric) di-methylation of arginine residues on histone and non-histone target proteins. PRMT signalling (and R methylation) drives cellular proliferation, cell invasion and metastasis, targeting (i) nuclear hormone receptor signalling, (ii) tumour suppressors, (iii) TGF-β and EMT signalling and (iv) alternative splicing and DNA/chromatin stability, influencing the clinical and survival outcomes in breast cancer. Emerging reports suggest that PRMTs are also implicated in the development of drug/endocrine resistance providing another prospective avenue for the treatment of hormone resistance and associated metastasis. The complexity of PRMT signalling is further underscored by the degree of alternative splicing and the scope of variant isoforms (with distinct properties) within each PRMT family member. The evolution of PRMT inhibitors, and the ongoing clinical trials of PRMT inhibitors against a subgroup of solid cancers, coupled to the track record of lysine methyltransferases inhibitors in phase I/II clinical trials against cancer underscores the potential therapeutic utility of targeting PRMT epigenetic enzymes to improve survival outcomes in aggressive and metastatic breast cancer.
journal_name
J Mol Endocrinoljournal_title
Journal of molecular endocrinologyauthors
Wang SM,Dowhan DH,Muscat GEOdoi
10.1530/JME-18-0224subject
Has Abstractpub_date
2019-04-01 00:00:00pages
R223-R237issue
3eissn
0952-5041issn
1479-6813pii
JME-18-0224journal_volume
62pub_type
杂志文章,评审abstract::Obesity is likely to be a multifactorial disease with an important genetic component. Animal models of genetic and experimentally induced obesity suggest that glucocorticoid receptor (GR) activity plays a role in the aetiology and maintenance of the obese state. Glucocorticoid activity appears to be essential for the ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0090295
更新日期:1992-12-01 00:00:00
abstract::There is evidence that insulin-like growth factor-binding protein (IGFBP-2), a modulator of the actions of IGFs, also has IGF-independent effects in human tumor cell lines. These involve specific binding of IGFBP-2 to alpha5beta1-integrin, followed by alterations in the phosphorylation status of downstream signaling m...
journal_title:Journal of molecular endocrinology
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doi:10.1677/jme.1.01955
更新日期:2006-08-01 00:00:00
abstract::Most pro-neuropeptides are processed by the prohormone convertases, PC1 and PC2. We previously reported that changes in thyroid status altered anterior pituitary PC1 mRNA and this regulation was due to triiodothyronine (T(3))-dependent interaction of thyroid hormone receptor (TR) with negative thyroid hormone response...
journal_title:Journal of molecular endocrinology
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doi:10.1677/jme.0.0330021
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abstract::Unbiased genomic screening analyses have highlighted novel immunomodulatory properties of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D). However, clearer interpretation of the resulting gene expression data is limited by cell model specificity. The aim of the current study was to provide a broader...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-17-0186
更新日期:2018-02-01 00:00:00
abstract::The mouse knockout of the estrogen receptor alpha (ERalpha) gene, known as alphaERKO, has been extensively used for several years to study the role and function of ERalpha. Residual estradiol binding capacity in uterine tissue of 5-10% raised doubts if this knockout is a genuine null mutation of ERalpha. Although alte...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0290281
更新日期:2002-12-01 00:00:00
abstract::Impaired insulin action has been associated with diabetes, dyslipidemia and atherosclerotic vascular disease. The expression of insulin resistance results from the interaction of environmental and genetic factors. Human hepatic lipase (HL) is a lipolytic enzyme that plays a role in the metabolism of several lipoprotei...
journal_title:Journal of molecular endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2005-04-01 00:00:00
abstract::Oestrogens have a major impact on reproductive function in both males and females. Two oestrogen receptor genes known as ERalpha (ESR1NR3A1) and ERbeta (ESR2NR3A2) have been cloned. Splice variant isoforms of the ERbeta gene have been identified in human, bovine and rodents and it has been suggested that the existence...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0320703
更新日期:2004-06-01 00:00:00
abstract::Orexin-A and -B are known to stimulate food intake in mammals. However, the critical roles of orexins in birds are not fully understood, since orexins have no stimulatory effect on food intake in the chicken. To understand the physiological role(s) of orexins in birds, we have cloned chicken orexin receptor (cOXR) cDN...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0310499
更新日期:2003-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-12-0200
更新日期:2013-06-04 00:00:00
abstract::A full-length transcript encoding a functional lamprey glycoprotein hormone receptor I (lGpH-R I, GenBank AY750688) was cloned from the testes of the sea lamprey, Petromyzon marinus, using the GpH-R protein fingerprint GLYCHORMONER from the PRINTS database. The present study is the first to identify a GpH-R transcript...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.02064
更新日期:2006-08-01 00:00:00
abstract::Whether insulin, at physiological concentrations, has direct effects on vascular smooth muscle cells (VSMCs) remains controversial. Our aim was to characterize the mechanism for insulin resistance in VSMCs. For comparison, the effects of IGF1 and IGF2 were also studied. Cultured human aortic smooth muscle cells (HASMC...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-09-0021
更新日期:2009-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-13-0182
更新日期:2013-12-20 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0070185
更新日期:1991-12-01 00:00:00
abstract::Human galanin (hGal) is an important neuro-modulator present in the brain, gastrointestinal system and the hypothalamo-pituitary axis. A specific receptor for hGal has been identified in various areas in human brain. A single class of high affinity binding sites was found on plasma membranes of the amygdala (Kd 0.23 n...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0130347
更新日期:1994-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-07-0070
更新日期:2007-10-01 00:00:00
abstract::Insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) in adipocytes is well known to traffic between high (HDM) and low (LDM) density microsomal fractions toward the plasma membrane (MF) under stimulation by insulin. However, its catalytic preference for aminoacyl substrates with N-terminal Leu or Cys is controversial....
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-14-0321
更新日期:2015-08-01 00:00:00
abstract::We have cloned a full length cDNA coding for the activin type IIB receptor (GactRIIB) from the goldfish ovary. GactRIIB shares 73 and 70% amino acid identity in the extracellular domain, and 78 and 80% identity in the intracellular domain with the type IIB receptors of the mouse and Xenopus respectively. The intracell...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0190047
更新日期:1997-08-01 00:00:00
abstract::Transportation of vitamin C [also called ascorbic acid (AA)], an important water-soluble antioxidant and cofactor in testis, requires glucose transporter family (GLUTs) and sodium/vitamin C cotransporter family (SVCT1 and SVCT2). There is so far scant information vis-à-vis the functional roles of SVCTs in testis, alth...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0230347
更新日期:1999-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0200261
更新日期:1998-04-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
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更新日期:2004-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0200141
更新日期:1998-02-01 00:00:00
abstract::Intracellular glucocorticoid (GC) receptor (GR) function determines tissue sensitivity to GCs and strongly affects the development of type 2 diabetes and obesity. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mediates intracellular steroid exposure to mouse liver GR by prereceptor reactivation of GCs and is...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0004
更新日期:2008-08-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1677/jme.1.01600
更新日期:2004-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0070021
更新日期:1991-08-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01857
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0270145
更新日期:2001-10-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-19-0011
更新日期:2019-05-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-14-0127
更新日期:2014-12-01 00:00:00
abstract::Secretion of parathyroid hormone-related protein (PTHrP) by sheep fetal parathyroid glands is reported to be an important factor in the maintenance of a placental calcium pump. The aim of the present study was to determine whether the developing rat parathyroid glands express PTHrP or parathyroid hormone (PTH), or bot...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0170149
更新日期:1996-10-01 00:00:00